Trichloroisocyanuric Acid → (R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-oxopyrrolidine-1-carboxylate

HRID 513017Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([C@H:10]2[CH2:14][C@@H:13]([OH:15])[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].ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O.CC1(C)N([O])C(C)(C)CCC1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([C:3]1[CH:4]=[C:5]([C@H:10]2[CH2:14][C:13](=[O:15])[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: -10 °C

Procedure

To a solution of (2R,4R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate (I-13A) (0.52 g, 1.7 mmol) and trichloroisocyanuric acid (0.4 g, 1.7 mmol) in DCM (20 mL) at −10° C. was added 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) (27 mg, 0.17 mmol). The mixture was stirred at −10° C. for 15 minutes, then to room temperature over 1 hour and subsequently poured into cold aqueous NaHCO3 containing ice while stirring. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and reduced to dryness to yield (R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-oxopyrrolidine-1-carboxylate (I-16). 1H NMR (400 MHz, CDCl3) δ 7.27-7.22 (m, 2 H), 7.12 (td, J=2.0, 8.8 Hz, 1 H), 5.33 (bs, 1 H), 4.06 (d, J=19.6 Hz, 1 H), 3.86 (d, J=19.6 Hz, 1 H), 3.15 (dd, J=10.0, 18.8 Hz, 1 H), 2.47 (dd, J=3.2, 18.8 Hz, 1 H), 1.35 (bs, 9 H). MS m/z 249.1 (M−56)+.

Workup

waitto room temperature over 1 hour
additioncontaining ice
stirringwhile stirring
customThe organic layer was separated
washwashed with brine
dry with materialdried over sodium sulfate
filtrationfiltered

Sources & evidence

ORD record: ord-b4b99483bf6b4e4884dca8d32cce755c
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102671B2

Reaction notes

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