Potassium Cyanide → (2R,4S)-tert-butyl 4-cyano-2-(3-fluorophenyl)-pyrrolidine-1-carboxylate

HRID 513024Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:12][C@@H:11](OS(C)(=O)=O)[CH2:10][N:9]2[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:5]=[CH:6][CH:7]=1.[C-:25]#[N:26].[K+]>CS(C)=O>[C:25]([C@@H:11]1[CH2:10][N:9]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH2:12]1)#[N:26]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of (2R,4R)-tert-butyl 2-(3-fluorophenyl)-4-((methylsulfonyl)oxy)pyrrolidine-1-carboxylate (I-29) (165 mg, 0.46 mmol), potassium cyanide (36 mg, 0.55 mmol) and DMSO (2 mL) was heated at 90° C. for 3 hours. After cooling, the reaction mixture was partitioned in Et2O and water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated to dryness. The residue was purified by silica gel chromatography, eluted with EtOAc/Hex (0-50% gradient) to yield (2R,4S)-tert-butyl 4-cyano-2-(3-fluorophenyl)-pyrrolidine-1-carboxylate (I-30) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.35-7.30 (m, 1 H), 7.02-6.93 (m, 2 H), 6.87 (d, J=9.6 Hz, 1 H), 5.16r1 (bs, 0.4 H), 5.00r2 (bs, 0.6 H), 4.00-3.73 (m, 2 H), 3.16 (bs, 1 H), 2.67 (bs, 1 H), 2.25-2.21 (m, 1 H), 1.49 (bs, 3 H), 1.23 (bs, 6 H). MS m/z 313.1 (M+23)+.

Workup

temperatureAfter cooling
customthe reaction mixture was partitioned in Et2O
washThe organic layer was washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated to dryness
customThe residue was purified by silica gel chromatography
washeluted with EtOAc/Hex (0-50% gradient)

Sources & evidence

ORD record: ord-38ec4274211742bab7cc6dbc9130738c
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102671B2

Reaction notes

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