Sodium Formate → Benzyl 2-(4-formylphenyl)pyrrolidine-1-carboxylate

HRID 1467770Notes

Reaction equation

HRID 1467770 reaction equation
[CH:1]([O-])=[O:2].[Na+].[C]=O.Br[C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:18][CH2:17][CH2:16][N:15]2[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])=[CH:10][CH:9]=1>CN(C=O)C>[CH:1]([C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:18][CH2:17][CH2:16][N:15]2[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])=[CH:10][CH:9]=1)=[O:2]

Participants

5

Reactant 3

HCID 2723810Sodium FormateHCID 59222259Phenylmethyl 2-(4-bromophenyl)-1-pyrrolidinecarboxylateHCID 178418416HCID 178418416, compound

Product 1

HCID 86639042Benzyl 2-(4-formylphenyl)pyrrolidine-1-carboxylateYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a 50 mL round-bottomed flask were placed Pd (PPh3)2Cl2 (70 mg, 0.1 mmol), and sodium formate (510 mg, 7.5 mmol) and purged with carbon monoxide. DMF (7 mL) and benzyl 2-(4-bromophenyl)pyrrolidine-1-carboxylate (1.8 g, 5 mmol) were added via syringes. The mixture was vigorously stirred at 100° C. under carbon monoxide atmosphere for 8 hrs. Then the reaction mixture was cooled to room temperature and partitioned between ether (100 mL) and water (15 mL). The organic phase was washed with water (3×15 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (silica gel, EtOAc:hexane=1:10) to give the title compound (0.31 g, yield 20%) as a colorless oil. LC-MS (ESI) m/z: 309 (M+1)+; 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 1.73-1.88 (m, 3H), 2.31-2.41 (m, 1H), 3.57-3.67 (m, 2H), 4.84-5.06 (m, 3H), 6.84-6.86 (m, 1H), 7.12-7.34 (m, 4H), 7.41-7.43 (d, J=8.0 Hz, 2H), 7.85-7.87 (d, J=8.0 Hz, 2H), 9.98-9.99 (d, J=6.0 Hz, 1H).

Workup

  1. customTo a 50 mL round-bottomed flask were placed
  2. temperatureThen the reaction mixture was cooled to room temperature
  3. custompartitioned between ether (100 mL) and water (15 mL)
  4. washThe organic phase was washed with water (3×15 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (silica gel, EtOAc:hexane=1:10)

Sources & evidence

ORD record
ord-c5e5b8096b4a43fe9e1b3d0df7ed0bd1
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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