Triethylamine → (2S,4R)-1-Phenyl-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic Acid Methyl Ester

HRID 1697551Notes

Reaction equation

HRID 1697551 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:21])[F:20])(=[O:12])=[O:11])[CH2:7][NH:6]1)=[O:4].[C:23]1(B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:20])[F:21])(=[O:11])=[O:12])[CH2:7][N:6]1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:4]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 66827Phenylboronic AcidHCID 66771131(2S,4R)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid methyl ester

Product 1

HCID 66770633(2S,4R)-1-Phenyl-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic Acid Methyl EsterYield 18.2%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,4R)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid methyl ester (see example xx) (1.03 g, 1.0 eq) in dry dichloromethane (25 mL) were added freshly powdered molecular sieves (2.88 g). Phenyl boronic acid (0.74 g, 2.0 eq) was added, followed by triethylamine (0.62 g, 2.0 eq) and copper(II)acetate (0.61 g, 1.1 eq). Oxygen gas was bubbled through the reaction mixture for 5 min. The flask was sealed with a rubber septum and left under an atmosphere of oxygen by means of a balloon. After stirring at room temperature for 24 h, the mixture was filtered and the filtrate was treated with water and filtered again. The phases were separated and the organic phase dried over sodium sulfate, filtered and evaporated. Purification by flash chromatography on silica gel with an heptane/ethyl acetate gradient yielded the title compound as a light yellow solid (0.23 g, 18%). MS (ESI): m/z=414.2 [M+H]+.

Workup

  1. customOxygen gas was bubbled through the reaction mixture for 5 min
  2. customThe flask was sealed with a rubber septum
  3. waitleft under an atmosphere of oxygen by means of a balloon
  4. filtrationthe mixture was filtered
  5. additionthe filtrate was treated with water
  6. filtrationfiltered again
  7. customThe phases were separated
  8. dry with materialthe organic phase dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customPurification by flash chromatography on silica gel with an heptane/ethyl acetate gradient

Sources & evidence

ORD record
ord-4447be48abcf402788d1d669a635423a
Source dataset
uspto-grants-2012_04
Patent number
US08163793B2

Reaction notes

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