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【结 构 式】 
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【分子编号】21199 【品名】(4S)-6-chloro-4-(2-cyclopropylethynyl)-2-(4-methoxyphenyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazine; 4-[(4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-yl]phenyl methyl ether 【CA登记号】 |
【 分 子 式 】C21H17ClF3NO2 【 分 子 量 】407.8194296 【元素组成】C 61.85% H 4.2% Cl 8.69% F 13.98% N 3.43% O 7.85% |
合成路线1
该中间体在本合成路线中的序号：(II)A new enantioselective synthesis of efavirenz starting from 2-[5-chloro-2-(4-methoxybenzylamino)phenyl]-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2(S)-ol (I), a previously described intermediate [see Drugs Fut 1998 23(2):133], has been reported: The oxidative cyclization of butynol (I) with dichlorodicyanobenzoquinone (DDQ) in toluene gives the benzoxazine (II) which, without isolation, is treated with NaOH and NaBH4 in methanol yielding the aminoalcohol (III). The acylation of (III) with methyl chloroformate (IV) and NaHCO3 in water affords the carbamate (V). Finally, this compound is cyclized by means of lithium tert-butoxide in tert-butyl methyl ether, or KOH in tert-butyl methyl ether/water.
| 【1】 Pierce, M.E.; et al.; Practical asymmetric synthesis of efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor. J Org Chem 1998, 63, 23, 8536. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 16578 | (2S)-2-[5-chloro-2-[(4-methoxybenzyl)amino]phenyl]-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol | C21H19ClF3NO2 | 详情 | 详情 | |
| (II) | 21199 | (4S)-6-chloro-4-(2-cyclopropylethynyl)-2-(4-methoxyphenyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazine; 4-[(4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-yl]phenyl methyl ether | C21H17ClF3NO2 | 详情 | 详情 | |
| (III) | 21200 | (2S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol | 209414-27-7 | C13H11ClF3NO | 详情 | 详情 |
| (IV) | 16993 | methyl chlorocarbonate;Carbonochloridic acid methyl ester；[(chlorocarbonyl)oxy]methane；methyl chloroformate | 79-22-1 | C2H3ClO2 | 详情 | 详情 |
| (V) | 21204 | methyl 4-chloro-2-[(1S)-3-cyclopropyl-1-hydroxy-1-(trifluoromethyl)-2-propynyl]phenylcarbamate | C15H13ClF3NO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)A new enantioselective synthesis of efavirenz starting from 2-[5-chloro-2-(4-methoxybenzylamino)phenyl]-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2(S)-ol (I), a previously described intermediate [see Drugs Fut 1998 23(2):133], has been reported: The oxidative cyclization of butynol (I) with dichlorodicyanobenzoquinone (DDQ) in toluene gives the benzoxazine (II) which, without isolation, is treated with NaOH and NaBH4 in methanol yielding the aminoalcohol (III). The acylation of (III) with p-nitrophenyl chloroformate (IV) and NaHCO3 in water affords the carbamate (V). Finally, this compound is cyclized by means of lithium tert-butoxide in tert-butyl methyl ether, or KOH in tert-butyl methyl ether/water.
| 【1】 Pierce, M.E.; et al.; Practical asymmetric synthesis of efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor. J Org Chem 1998, 63, 23, 8536. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 16578 | (2S)-2-[5-chloro-2-[(4-methoxybenzyl)amino]phenyl]-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol | C21H19ClF3NO2 | 详情 | 详情 | |
| (II) | 21199 | (4S)-6-chloro-4-(2-cyclopropylethynyl)-2-(4-methoxyphenyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazine; 4-[(4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-yl]phenyl methyl ether | C21H17ClF3NO2 | 详情 | 详情 | |
| (III) | 21200 | (2S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol | 209414-27-7 | C13H11ClF3NO | 详情 | 详情 |
| (IV) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |
| (V) | 21203 | 4-nitrophenyl 4-chloro-2-[(1S)-3-cyclopropyl-1-hydroxy-1-(trifluoromethyl)-2-propynyl]phenylcarbamate | C20H14ClF3N2O5 | 详情 | 详情 |