Aluminium lithium hydride → 2-(4-Fluoro-phenyl)-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1644818Notes

Reaction equation

HRID 1644818 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C[O:8][C:9]([C:11]1([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:15][CH2:14][CH2:13][N:12]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=O>C(OCC)C>[C:19]([O:18][C:16]([N:12]1[CH2:13][CH2:14][CH2:15][C:11]1([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[CH2:9][OH:8])=[O:17])([CH3:22])([CH3:20])[CH3:21]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 667735252-(4-Fluoro-phenyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 667735772-(4-Fluoro-phenyl)-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 86.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a suspension of lithiumaluminiumhydride (1.5 g) in dry diethyl ether (25 mL) at −20° C. was added dropwise a solution of 2-(4-fluoro-phenyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (4.25 g) in dry diethyl ether (20 mL) over 10 minutes. The reaction was stirred at −20° C. for 20 minutes and followed by TLC. After 30 minutes the reaction was quenched at −20° C. by adding saturated aqueous sodium sulfate solution dropwise until the lithium aluminium hydride reagent was fully quenched. Further solid sodium sulfate was added to the slurry and the mixture was allowed to warm to ambient temperature. The slurry was filtered and the solid was washed with further diethyl ether. The filtrate was collected and the diethyl ether was evaporated in vacuo to afford the desired 2-(4-fluoro-phenyl)-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (3.37 g, MS (ES+): 296.3 (MH+)) as a colourless oil.

Workup

  1. customAfter 30 minutes the reaction was quenched at −20° C.
  2. additionby adding saturated aqueous sodium sulfate solution dropwise until the lithium aluminium hydride reagent
  3. customwas fully quenched
  4. additionFurther solid sodium sulfate was added to the slurry
  5. temperatureto warm to ambient temperature
  6. filtrationThe slurry was filtered
  7. washthe solid was washed with further diethyl ether
  8. customThe filtrate was collected
  9. customthe diethyl ether was evaporated in vacuo

Sources & evidence

ORD record
ord-d5f324281e22475484adcd0e1ee5df21
Source dataset
uspto-grants-2012_02
Patent number
US08124636B2

Reaction notes

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