Potassium Carbonate → 4-[(R)-3-(3,5-Dichloro-4'-methoxycarbonyl-biphenyl-4-ylmethyl)-2-oxo-pyrrolidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1171153Notes

Reaction equation

HRID 1171153 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:18][CH2:17][CH:16]([CH2:19][C:20]3[C:25]([Cl:26])=[CH:24][C:23](OS(C(F)(F)F)(=O)=O)=[CH:22][C:21]=3[Cl:35])[C:15]2=[O:36])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:37][O:38][C:39]([C:41]1[CH:46]=[CH:45][C:44](B(O)O)=[CH:43][CH:42]=1)=[O:40].C([O-])([O-])=O.[K+].[K+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH2:18][CH2:17][C@@H:16]([CH2:19][C:20]3[C:25]([Cl:26])=[CH:24][C:23]([C:44]4[CH:45]=[CH:46][C:41]([C:39]([O:38][CH3:37])=[O:40])=[CH:42][CH:43]=4)=[CH:22][C:21]=3[Cl:35])[C:15]2=[O:36])[CH2:12][CH2:13]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 866291214-[3-(2,6-Dichloro-4-trifluoromethanesulfonyloxy-benzyl)-2-oxo-pyrrolidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666715514-[(R)-3-(3,5-Dichloro-4'-methoxycarbonyl-biphenyl-4-ylmethyl)-2-oxo-pyrrolidin-1-yl]-piperidine-1-carboxylic acid tert-butyl esterYield 88%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Treat a solution of 4-[3-(2,6-Dichloro-4-trifluoromethanesulfonyloxy-benzyl)-2-oxo-pyrrolidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (Preparation 15) (0.5 g, 0.9 mmol), 4-methoxycarbonylphenylboronic acid (0.31 g, 1.7 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.1 g, 0.1 mmol) in DME (5 mL) with 2M aqueous K2CO3 (1.3 mL), heat the reaction to 80° C., and stir overnight. Cool the reaction and quench with 1N HCl. Extract the aqueous with EtOAc. Wash the organic with brine, dry over MgSO4, and filter. Purify the crude by silica gel column chromatography using Hexanes:EtOAc to elute the pure product. Remove the solvent to afford 0.43 g (88%) of desired product. MS (m/e): 583 (M+Na+).

Workup

  1. temperatureheat
  2. customthe reaction to 80° C.
  3. temperatureCool
  4. customthe reaction
  5. customquench with 1N HCl
  6. extractionExtract the aqueous with EtOAc
  7. washWash the organic with brine
  8. dry with materialdry over MgSO4
  9. filtrationfilter
  10. customPurify the crude by silica gel column chromatography
  11. washEtOAc to elute the pure product
  12. customRemove the solvent

Sources & evidence

ORD record
ord-2284cfd9b20f424b95485fc93d29f6fe
Source dataset
uspto-grants-2010_11
Patent number
US07829582B2

Reaction notes

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