(R)-beta-aminophenethyl alcohol → (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid

HRID 1516623Notes

Reaction equation

HRID 1516623 reaction equation
C1([C@H](CO)N)C=CC=CC=1.[F:11][C:12]1[CH:13]=[C:14]([CH:32]=[CH:33][CH:34]=1)[CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[C:27](=[O:28])[CH2:26][CH:25]([C:29]([OH:31])=[O:30])[CH2:24]2)=[CH:19][CH:18]=1>C(#N)C.O>[F:11][C:12]1[CH:13]=[C:14]([CH:32]=[CH:33][CH:34]=1)[CH2:15][O:16][C:17]1[CH:18]=[CH:19][C:20]([N:23]2[C:27](=[O:28])[CH2:26][C@H:25]([C:29]([OH:31])=[O:30])[CH2:24]2)=[CH:21][CH:22]=1

Participants

4

Reactant 2

HCID 2724025(R)-beta-aminophenethyl alcohol2×HCID 21920015Rac-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid

Product 1

HCID 67409315(S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acidYield 44.1%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent2×

Procedure

The salt of the (S)-(II) compound with (R)-(−)-2-phenylglycinol was prepared in an analogous manner as described in Example 2 a) from rac-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (5 g, 15.2 mmol) in acetonitrile/water 95:5 (50 mL) using a solution of only 1.46 g (R)-(−)-2-phenylglycinol (10.6 mmol, 0.7 eq) in acetonitrile/water 95:5 (3.3 mL). From the salt (3.2 g, 45% based on racemic acid) obtained in 99.7:0.3 diastereomeric ratio the (S)-(II) compound was liberated and purified in a similar manner as described in Example 2b) to afford (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (2.21 g, 44% based on racemic acid) in high purity (HPLC: 99.4% area) and with >99.9:0.1% er.

Workup

  1. customFrom the salt (3.2 g, 45% based on racemic acid) obtained in 99.7:0.3 diastereomeric ratio the (S)-(II) compound
  2. custompurified in a similar manner

Sources & evidence

ORD record
ord-559a7b0e287b41d69cfc8558aefa69ff
Source dataset
uspto-grants-2012_07
Patent number
US08227505B2

Reaction notes

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