Sodium hydride → tert-butyl (S)-3-(2-bromo-5-fluorobenzyloxy)pyrrolidine-1-carboxylate

HRID 928070Notes

Reaction equation

HRID 928070 reaction equation
[H-].[Na+].[OH:3][C@H:4]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]1.[Br:16][C:17]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:18]=1[CH2:19]Br>C1COCC1>[Br:16][C:17]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:18]=1[CH2:19][O:3][C@H:4]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5179721-Bromo-2-(bromomethyl)-4-fluorobenzeneHCID 854055tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 68923111tert-butyl (S)-3-(2-bromo-5-fluorobenzyloxy)pyrrolidine-1-carboxylateYield 100.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% oil dispersion, 0.24 g) was added to a stirred solution of tert-butyl (S)-3-hydroxypyrrolidine-1-carboxylate (0.935 g) in THF (15 mL) and the mixture was stirred for 5 minutes. 2-Bromo-5-fluorobenzyl bromide (1.608 g) was added and stirring was continued for 20 hours. The resultant suspension was filtered and the filtrate was evaporated to dryness. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-15% to give tert-butyl (S)-3-(2-bromo-5-fluorobenzyloxy)-pyrrolidine-1-carboxylate (1.88 g) as a colourless oil.

Workup

  1. stirringstirring
  2. waitwas continued for 20 hours
  3. filtrationThe resultant suspension was filtered
  4. customthe filtrate was evaporated to dryness
  5. customThe residue was purified by chromatography on silica
  6. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-15%

Sources & evidence

ORD record
ord-fc74d8ab5ee94ea7b305504110d3b307
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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