Pyrrolidine → HCID 59840098, compound

HRID 1365923Notes

Reaction equation

HRID 1365923 reaction equation
[Br:1][CH2:2][C:3](Cl)=[O:4].[F:6][C:7]([F:38])([F:37])[C:8]1[CH:9]=[C:10]([C:18]([CH3:36])([CH3:35])[C:19]([N:21]([C@H:23]2[C@H:27]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[CH2:26][NH:25][CH2:24]2)[CH3:22])=[O:20])[CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=1.N1CCCC1.C(N(C(C)C)C(C)C)C>C(Cl)Cl>[F:17][C:14]([F:15])([F:16])[C:12]1[CH:11]=[C:10]([C:18]([CH3:35])([CH3:36])[C:19]([N:21]([C@H:23]2[C@H:27]([C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[CH2:26][N:25]([C:3](=[O:4])[CH2:2][Br:1])[CH2:24]2)[CH3:22])=[O:20])[CH:9]=[C:8]([C:7]([F:38])([F:37])[F:6])[CH:13]=1

Participants

6

Reactant 4

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 89602Bromoacetyl chlorideHCID 59840130HCID 59840130, compound

Product 1

HCID 59840098HCID 59840098, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of bromo-acetyl chloride (0.80 g, 4 mmol) in CH2Cl2 (5 ml) at 0° C. was added over 1 hour a solution of rac-2-(3,5-bis-trifluoromethyl-phenyl)-N-[(3S,4R)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-N-methyl-isobutyramide (pyrrolidine interm. VII-4 described herein above, 0.94 g, 1.97 mmol) and ethyl-diisopropyl-amine (0.37 ml, 2.17 mmol) in CH2Cl2 (10 mL). The reaction was stirred over night, quenched by addition of an aqueous solution of NaHCO3, and the product extracted with CH2Cl2. Purification by flash chromatography (SiO2, EtOAc/Hx 1:1) yielded 0.83 g (70%) of rac-2-(3,5-bis-trifluoromethyl-phenyl)-N-[(3S,4R)-1-(2-bromo-acetyl)-4-(4-fluoro-phenyl)-pyrrolidin-3-yl]-N-methyl-isobutyramide as a white foam.

Workup

  1. customquenched by addition of an aqueous solution of NaHCO3
  2. extractionthe product extracted with CH2Cl2
  3. customPurification by flash chromatography (SiO2, EtOAc/Hx 1:1)

Sources & evidence

ORD record
ord-05e492f3e12e4ed6a9cc85c12d8bd510
Source dataset
uspto-grants-2011_02
Patent number
US07893062B2

Reaction notes

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