(Diethylamino)sulfur trifluoride → (2R,4S)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-fluoropyrrolidine-1-carboxylate

HRID 513014Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([C@H:10]2[CH2:14][C@@H:13](O)[CH2:12][N:11]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:6]=[C:7]([F:9])[CH:8]=1)#[N:2].CCN(S(F)(F)[F:29])CC>C(Cl)Cl>[C:1]([C:3]1[CH:4]=[C:5]([C@H:10]2[CH2:14][C@H:13]([F:29])[CH2:12][N:11]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:6]=[C:7]([F:9])[CH:8]=1)#[N:2]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of (2R,4R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate (I-13A) (0.7 g, 2.3 mmol) in DCM (4 mL) in a plastic bottle at −78° C. was added DAST (0.6 mL, 4.6 mmol). The reaction was stirred at −78° C. for 2 hours and then loaded directly onto silica gel and purified by column chromatography with EtOAc/hexanes gradient as eluant to yield (2R,4S)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-fluoropyrrolidine-1-carboxylate (I-14). 1H NMR (400 MHz, CDCl3) δ 7.35 (s, 1 H), 7.30-7.16 (m, 2 H), 5.25 (d, J=52.0 Hz, 1 H), 5.06-4.86 (m, 1 H), 4.20-3.98 (m, 1 H), 3.72 (dd, J=11.6, 38.8 Hz, 1 H), 2.80-2.66 (m, 1 H), 2.06-1.78 (m, 1 H), 1.45 (bs, 3 H), 1.19 (bs, 6 H). MS m/z 331.1 (M+23)+.

Workup

custompurified by column chromatography with EtOAc/hexanes gradient as eluant

Sources & evidence

ORD record: ord-128ab64c7d614813907dd8a389e5b0e8
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102671B2

Reaction notes

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