2,5-Dimethylpyrrolidine, (2R,5R)- → Methyl 2-(((2R,5R)-2,5-dimethyl-1-pyrrolidinyl)methyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-carboxylate

HRID 1662474Notes

Reaction equation

HRID 1662474 reaction equation
C([BH3-])#N.[Na+].[F:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:7]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20]([O:22][CH3:23])=[O:21])=[CH:16][C:15]=1[CH:24]=O.[CH3:26][C@@H:27]1[CH2:31][CH2:30][C@@H:29]([CH3:32])[NH:28]1>CO.CCOC(C)=O>[CH3:26][C@@H:27]1[CH2:31][CH2:30][C@@H:29]([CH3:32])[N:28]1[CH2:24][C:15]1[CH:16]=[C:17]([C:20]([O:22][CH3:23])=[O:21])[CH:18]=[CH:19][C:14]=1[C:7]1[CH:8]=[C:9]([O:12][CH3:13])[CH:10]=[CH:11][C:6]=1[F:5]

Participants

6

Reactant 3

HCID 6417672,5-Dimethylpyrrolidine, (2R,5R)-HCID 5003444Sodium cyanoborohydrideHCID 574676302'-Fluoro-2-formyl-5'-methoxy-biphenyl-4-carboxylic acid methyl ester

Product 1

HCID 57705891Methyl 2-(((2R,5R)-2,5-dimethyl-1-pyrrolidinyl)methyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-carboxylateYield 13.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Sodium cyanoborohydride (0.071 g, 1.1 mmol) was added to a solution of 66.60C (0.180 g, 0.62 mmol) and (2R,5R)-2,5-dimethylpyrrolidine (available from Aldrich) (0.073 g, 0.74 mmol) in MeOH (3 mL). The reaction was stirred at 110° C. for 30 minutes and then was diluted with EtOAc (100 mL). The mixture was washed with an aqueous Na2CO3 solution and brine, and dried over anhydrous sodium sulfate. After filtration, solvent was removed, and the residue was purified by flash chromatography (silica gel, 1:6 EtOAc/hexane) and gave 66.71A (32 mg).

Workup

  1. washThe mixture was washed with an aqueous Na2CO3 solution and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationAfter filtration, solvent
  4. customwas removed
  5. customthe residue was purified by flash chromatography (silica gel, 1:6 EtOAc/hexane)

Sources & evidence

ORD record
ord-366654af05f644e59206834295c4caf3
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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