1-Phenethylamine, (-)- → (s)-(+)-3-{1-(1,3-Benzodioxol-5-yl)-2-[(2-methoxy4-methylphenyl)-sulfonylamino]-2-oxoethyl}-1-methyl-1h-indole-6-carboxylic acid

HRID 322092ノート

反応式

HRID 322092 の反応式
C[C@H](N)C1C=CC=CC=1.[O:10]1[C:14]2[CH:15]=[CH:16][C:17]([CH:19]([C:35]3[C:43]4[C:38](=[CH:39][C:40]([C:44]([OH:46])=[O:45])=[CH:41][CH:42]=4)[N:37]([CH3:47])[CH:36]=3)[C:20]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=3[O:33][CH3:34])(=[O:25])=[O:24])=[O:21])=[CH:18][C:13]=2[O:12][CH2:11]1>O1CCCC1.COCCOC>[O:10]1[C:14]2[CH:15]=[CH:16][C:17]([C@@H:19]([C:35]3[C:43]4[C:38](=[CH:39][C:40]([C:44]([OH:46])=[O:45])=[CH:41][CH:42]=4)[N:37]([CH3:47])[CH:36]=3)[C:20]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=3[O:33][CH3:34])(=[O:24])=[O:25])=[O:21])=[CH:18][C:13]=2[O:12][CH2:11]1

参加物

5

反応物 2

HCID 758181-Phenethylamine, (-)-2 回HCID 22009947HCID 22009947、化合物

生成物 1

HCID 9807200(s)-(+)-3-{1-(1,3-Benzodioxol-5-yl)-2-[(2-methoxy4-methylphenyl)-sulfonylamino]-2-oxoethyl}-1-methyl-1h-indole-6-carboxylic acid

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
55 °C

実験手順

(S)-(−)-α-Methylbenzylamine (0.53 kg) was added over a period of 15 minutes to a stirred suspension of 3-{1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy4-methylphenyl)sulfonylamino]-2-oxoethyl}-1-methyl-1H-indole-6-carboxylic acid (from step (c), 1.17 kg, 2.18 moles) in tetrahydrofuran (6.5 liters, 5.5 ml/g) and 1,2-dimethoxyethane (6.5 liters, 5.5 ml/g) at 60° C. under a nitrogen atmosphere. The resulting solution was allowed to cool to 55° C., seeded with 13.6 g of the (S)-(−)-α-methylbenzylamine salt of the title compound of Example 1 (prepared by conventional methods) and stirred for 24 h. The resulting suspension was allowed to cool to 45° C. over a period of 48 h and stirred at this temperature for an additional 48 h. The suspension was allowed to cool to room temperature and the precipitated (S)-(−)-α-methylbenzylamine salt (of the title compound) collected by filtration (1.316 kg, 84%, ratio of (S)-(−)-α-methylbenzylamine to (S)-(+)-acid in the salt 1.5:1). The salt was partitioned between ethyl acetate (6.8 liters), tetrahydrofuran (1.4 liters) and 1M hydrochloric acid (6.8 liters) and the organic phase was separated and then washed with 1M hydrochloric acid (3×0.9 liters) and water (2×0.7 liters). The organic phase was dried by azeotropic distillation with ethyl acetate at constant volume, concentrated to a volume of 3.5 liters and then n-hexane (3.5 liters) added. The precipitated product was granulated at 0° C. for 1 h and filtered to give the title compound as a white crystalline solid (0.936 kg, 91.6%). The enantiomeric excess of the compound was found to be >94% using chiral stationary phase HPLC.

出典と根拠

ORDレコード
ord-000bd18992774176af086161834d1fa1
出典データセット
uspto-grants-2001_04
特許番号
US06211223B1

反応ノート

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