Lithium borohydride → tert-Butyl (2R,4S)-4-fluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 732351Notes

Reaction equation

HRID 732351 reaction equation
[BH4-].[Li+].C[O:4][C:5]([C@H:7]1[CH2:11][C@H:10]([F:12])[CH2:9][N:8]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=O>C1COCC1>[C:16]([O:15][C:13]([N:8]1[CH2:9][C@@H:10]([F:12])[CH2:11][C@@H:7]1[CH2:5][OH:4])=[O:14])([CH3:19])([CH3:18])[CH3:17]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 584838511-tert-butyl 2-methyl (2R,4S)-4-fluoropyrrolidine-1,2-dicarboxylate

Product 1

HCID 58483823tert-Butyl (2R,4S)-4-fluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylateYield 101.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add lithium borohydride (0.43 g, 19.6 mmol) to an ice cold solution of 4-(S)-fluoropyrrolidine-N1,2-(R)-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (3.9 g, 13.08 mmol) in THF (50 mL). Warm to room temperature over 18 h. Cool in ice bath. Slowly add acetic acid (3 mL) and water and extract with ethyl acetate. Wash extract with water, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a thick oil (2.90 g, 100%).

Workup

  1. temperatureCool in ice bath
  2. extractionSlowly add acetic acid (3 mL) and water and extract with ethyl acetate
  3. washWash
  4. extractionextract with water, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride
  5. dry with materialdry (magnesium sulfate)
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with hexanes and ethyl acetate)

Sources & evidence

ORD record
ord-48fa2eaefc204c9eafbde45da13178f8
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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