Sodium hydride → HCID 118331283, compound

HRID 1754262Notes

Reaction equation

HRID 1754262 reaction equation
[O:1]=[C:2]1[C@@H:6]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:5][CH2:4][NH:3]1.[H-].[Na+].FC(F)(F)S(O[CH2:23][C:24]([F:27])([F:26])[F:25])(=O)=O>CN(C=O)C>[O:1]=[C:2]1[C@@H:6]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:5][CH2:4][N:3]1[CH2:23][C:24]([F:27])([F:26])[F:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 10750535(S)-tert-Butyl (2-oxopyrrolidin-3-yl)carbamate

Product 1

HCID 118331283HCID 118331283, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-tert-butyl (2-oxopyrrolidin-3-yl)carbamate (250 mg, 1.25 mmol) in DMF (5 mL) at 0° C. was added sodium hydride (52.9 mg, 1.32 mmol). After stirring at rt for 1 h, 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.18 mL, 1.25 mmol) was added then the reaction mixture was allowed to warm to rt and stirred for 3.5 h. The reaction mixture was concentrated under reduced pressure and the residue purified on silica gel eluting with 0 to 75% EtOAc/DCM to give Compound 91a (95 mg, 27% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 5.11 (br. s., 1H), 4.24 (br. s., 1H), 4.07 (dq, J=15.0, 9.2 Hz, 1H), 3.91-3.67 (m, 1H), 3.63-3.37 (m, 2H), 2.84-2.47 (m, 1H), 2.12-1.84 (m, 1H), 1.53-1.42 (m, 9H). COSY NMR shows coupling of NH at 5.11 ppm to methine at 4.24 ppm, confirming regioselectivity of alkylation on the pyrrolidinone nitrogen. US 2009/760005 A1.

Workup

  1. temperatureto warm to rt
  2. stirringstirred for 3.5 h
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe residue purified on silica gel eluting with 0 to 75% EtOAc/DCM

Sources & evidence

ORD record
ord-437e82715927499583dd73e8b4242ea2
Source dataset
uspto-grants-2015_10
Patent number
US09169240B2

Reaction notes

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