Water → (3R)-4-{[(1R)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid

HRID 2040499Notes

Reaction equation

HRID 2040499 reaction equation
C1C([C@H](CN)CC(O)=[O:10])=CC=C(Cl)C=1.O.[CH3:16][CH:17]([CH3:42])[C@@H:18]([O:36][C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])[O:19][C:20]([NH:22][CH2:23][C@@H:24]([C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[CH2:25][C:26]([OH:28])=[O:27])=[O:21].[CH3:43][CH:44]([CH3:69])[C@H:45]([O:63][C:64](=[O:68])[CH:65]([CH3:67])[CH3:66])[O:46][C:47]([NH:49][CH2:50][C@@H:51]([C:56]1[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][CH:57]=1)[CH2:52][C:53]([OH:55])=[O:54])=[O:48]>C(OC)(C)(C)C>[OH2:10].[CH3:16][CH:17]([CH3:42])[C@@H:18]([O:36][C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])[O:19][C:20]([NH:22][CH2:23][C@@H:24]([C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[CH2:25][C:26]([OH:28])=[O:27])=[O:21].[CH3:43][CH:44]([CH3:69])[C@@H:45]([O:63][C:64](=[O:68])[CH:65]([CH3:67])[CH3:66])[O:46][C:47]([NH:49][CH2:50][C@@H:51]([C:56]1[CH:61]=[CH:60][C:59]([Cl:62])=[CH:58][CH:57]=1)[CH2:52][C:53]([OH:55])=[O:54])=[O:48].[CH3:16][CH:17]([CH3:42])[C@H:18]([O:36][C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])[O:19][C:20]([NH:22][CH2:23][C@@H:24]([C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)[CH2:25][C:26]([OH:28])=[O:27])=[O:21]

Participants

7

Reactant 4

HCID 962WaterHCID 44602ArbaclofenHCID 11281011Arbaclofen PlacarbilHCID 15974653(3R)-4-{[(1R)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid

Product 2

HCID 15974653(3R)-4-{[(1R)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acidHCID 71496727(3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxyl)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid hemihydrate

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

In certain embodiments, crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid hemihydrate (1b) can be prepared by steps comprising providing a first solution comprising 1-((2,5-dioxopyrrolidin-1-yl-oxycarbonyloxy)-2-methylpropyl-2-methylpropanoate (3) prepared as a racemic mixture, (R)-baclofen (2), about 65% v/v water and about 35% v/v methyl tert-butyl ether; increasing the temperature of the first solution to create a second solution comprising (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid (1) and (3R)-4-{[(1R)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid (4); and decreasing the temperature of the second solution to provide crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid hemihydrate (1b) and (3R)-4-{[(1R)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid (4).

Workup

  1. temperatureincreasing the temperature of the first solution

Sources & evidence

ORD record
ord-60064571b94a4fe58ceba64f0bf0d1d6
Source dataset
uspto-grants-2013_11
Patent number
US08580850B2

Reaction notes

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