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 322092Notes

Reaction equation

HRID 322092 reaction equation
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

Participants

5

Reactant 2

HCID 758181-Phenethylamine, (-)-2×HCID 22009947HCID 22009947, compound

Product 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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
55 °C

Procedure

(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.

Sources & evidence

ORD record
ord-000bd18992774176af086161834d1fa1
Source dataset
uspto-grants-2001_04
Patent number
US06211223B1

Reaction notes

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