Hydrochloric Acid → (4R)-4-Fluoro-1-methyl-L-proline

HRID 1402300Notes

Reaction equation

HRID 1402300 reaction equation
[F:1][C@H:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.[CH2:10]=O.Cl>[Pd]>[F:1][C@H:2]1[CH2:6][N:5]([CH3:10])[C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 11902999(4R)-4-Fluoro-L-proline

Product 1

HCID 55300764(4R)-4-Fluoro-1-methyl-L-prolineYield 54.2%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

A solution of (2S,4R)-4-fluoropyrrolidine-2-carboxylic acid (1.00 g, 7.52 mmol), formaldehyde (37% wt in water, 1.00 mL, 30.8 mmol), 12N HCl (0.5 mL) in IMS (38 mL) was purged with argon. To the solution was added Pd/C (100 mg), then the flask was evacuated and filled with H2 the resulting suspension was stirred at RT for 3 d. The reaction mixture was passed through a pad of Celite and the mixture was concentrated in vacuo to give the title compound as a pale yellow gum (600 mg, 54%). 1H NMR (300 MHz, d6-DMSO): 2.29-2.37 (1H, m), 2.63-2.67 (1H, m), 2.97 (3H, s), 3.44-3.53 (1H, m), 4.00-4.04 (1H, m), 4.58 (1H, dd, J 11.6, 7.11), 5.41-5.45 (1H, m).

Workup

  1. customthe flask was evacuated
  2. additionfilled with H2 the resulting suspension
  3. concentrationthe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-102d7cde2a1441899be140503c9fbf3f
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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