Tetrabutylammonium Fluoride → (R)-tert-Butyl 3-(fluoromethyl)-pyrrolidine-1-carboxylate

HRID 717503Notes

Reaction equation

HRID 717503 reaction equation
CS(O[CH2:6][C@@H:7]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8]1)(=O)=O.[F-:19].C([N+](CCCC)(CCCC)CCCC)CCC>>[F:19][CH2:6][C@@H:7]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8]1

Participants

3

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 40479140(R)-tert-butyl 3-(((methylsulfonyl)oxy)methyl)pyrrolidine-1-carboxylate

Product 1

HCID 58951460(R)-tert-Butyl 3-(fluoromethyl)-pyrrolidine-1-carboxylate

Procedure

Tetrabutylammonium fluoride (1M solution in THF, 530 mL) was added to (R)-tert-butyl 3-(((methylsulfonyl)oxy)methyl)pyrrolidine-1-carboxylate (30 g from previous step) and the resulting mixture was refluxed overnight. After cooling, the solvent was removed and the residue was partitioned between 10% aqueous citric acid and dichloromethane. The organic layer was washed with water, dried over sodium sulfate, filtered and the solvent was removed on a rotary evaporator. The residue was purified by flash chromatography on a silica gel column (0 to 50% ethyl acetate/hexanes) to afford 14.3 g of (R)-tert-butyl 3-(fluoromethyl)pyrrolidine-1-carboxylate as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 4.49-4.41 (m, 1H), 4.37-4.29 (m, 1H), 3.40-3.28 (m, 2H), 3.24-3.18 (m, 1H), 3.02-2.98 (m, 1H), 2.58-2.52 (m, 1H), 1.95-1.88 (m, 1H), 1.67-1.54 (m, 1H), 1.38 (s, 9H).

Workup

  1. temperaturethe resulting mixture was refluxed overnight
  2. temperatureAfter cooling
  3. customthe solvent was removed
  4. customthe residue was partitioned between 10% aqueous citric acid and dichloromethane
  5. washThe organic layer was washed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed on a rotary evaporator
  9. customThe residue was purified by flash chromatography on a silica gel column (0 to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7c3fecdcc65f4b609e7343cc1b1adddf
Source dataset
uspto-grants-2015_11
Patent number
US09193714B2

Reaction notes

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