2-[4-[oxiranylmethoxy]phenyl]acetamide -Drug Synthesis Database

【结构式】

【分子编号】51072

【品名】2-[4-[oxiranylmethoxy]phenyl]acetamide

【CA登记号】

【分子式】C₁₁H₁₃NO₃

【分子量】207.22916

【元素组成】C 63.76% H 6.32% N 6.76% O 23.16%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

Condensation of acetamide (I) with (R)-epichlorohydrin (II) by means of either NaOH, LiOH or NaOH/benzyltrimethylammonium chloride (BTA-Cl) in H2O yields a mixture of epoxypropane (III) and chloropropanol derivative (IV) that can be converted into the desired product either by direct coupling with isopropylamine (V) in MeOH, or by first reaction of the mixture (III)/(IV) with NaOH to give (S)-(III) and next coupling with (V) as described above (1-3). Alternatively, derivative (S)-(III) can also be obtained by coupling of glycidyl nosylate (VI) with acetamide (I) by means of CsF in DMF.

参考文献中间体

合成目标

【1】 Kitaori, K.; et al.; A practical synthesis of optically active atenolol from chiral epichlorohydrin. Chem Pharm Bull 1997, 45, 2, 412.
【2】 Kitaori, K.; et al.; CsF in organic synthesis. Regioselective nucleophilic reactions of phenols with oxiranes leading to enantiopure beta-blockers. Tetrahedron 1999, 55, 50, 14381.
【3】 Kitaori, K.; et al.; Convenient preparation of enantiopure atenolol by means of preferential crystallization. Chem Pharm Bull 1998, 46, 3, 505.
【4】 Saragai, N.; Takehira, Y.; Kitaori, K. (Daiso Co., Ltd.); Process for producing optically active atenolol and intermediate thereof. EP 0435068 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(S)-(III)	51074	2-[4-[(2S)oxiranylmethoxy]phenyl]acetamide		C₁₁H₁₃NO₃	详情	详情
(I)	32754	p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide	17194-82-0	C₈H₉NO₂	详情	详情
(II)	38067	(2R)-2-(Chloromethyl)oxirane; (R)-Epichlorohydrin	51594-55-9	C₃H₅ClO	详情	详情
(III)	51072	2-[4-[oxiranylmethoxy]phenyl]acetamide		C₁₁H₁₃NO₃	详情	详情
(IV)	51073	2-(4-[[(2R)-3-chloro-2-hydroxypropyl]oxy]phenyl)acetamide		C₁₁H₁₄ClNO₃	详情	详情
(V)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情
(VI)	45631	(2S)oxiranylmethyl 4-nitrobenzenesulfonate		C₉H₉NO₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Treatment of sodium phenoxide derivative (I) with Amberlite IRA-400 (containing quaternary ammonium groups) provides resin (II), which is then coupled with epichlorohydrin (III) in refluxing MeOH to afford arylepoxyether (IV). Finally, (S)-atenolol is obtained by reaction of (IV) with isopropylamine (V) in refluxing MeOH.

参考文献中间体

合成目标

【1】 Damle, S.V.; et al.; One pot synthesis of (±)/(S)-atenolol and (±)/(S)-propranolol by employing polymer supported reagent. Synth Commun 1999, 29, 10, 1639.

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)	51083	sodium 4-(2-amino-2-oxoethyl)benzenolate		C₈H₈NNaO₂	详情	详情
(II)	51084	N,N,N-trimethylmethanaminium 4-(2-amino-2-oxoethyl)benzenolate		C₁₂H₂₀N₂O₂	详情	详情
(III)	38067	(2R)-2-(Chloromethyl)oxirane; (R)-Epichlorohydrin	51594-55-9	C₃H₅ClO	详情	详情
(IV)	51072	2-[4-[oxiranylmethoxy]phenyl]acetamide		C₁₁H₁₃NO₃	详情	详情
(V)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情

Extended Information