Aluminium lithium hydride → (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(3-hydroxy-propyl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 409460Notes

Reaction equation

HRID 409460 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[C:7]([O:11][C:12]([N:14]1[CH2:18][C@@H:17]([N:19]([CH2:32][C:33]2[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[C:35]([C:43]([F:46])([F:45])[F:44])[CH:34]=2)[C:20]2[N:25]=[CH:24][C:23]([CH2:26][CH2:27][C:28](OC)=[O:29])=[CH:22][N:21]=2)[CH2:16][C@H:15]1[CH2:47][CH3:48])=[O:13])([CH3:10])([CH3:9])[CH3:8]>C(OCC)C>[C:7]([O:11][C:12]([N:14]1[CH2:18][C@@H:17]([N:19]([CH2:32][C:33]2[CH:34]=[C:35]([C:43]([F:46])([F:44])[F:45])[CH:36]=[C:37]([C:39]([F:40])([F:41])[F:42])[CH:38]=2)[C:20]2[N:21]=[CH:22][C:23]([CH2:26][CH2:27][CH2:28][OH:29])=[CH:24][N:25]=2)[CH2:16][C@H:15]1[CH2:47][CH3:48])=[O:13])([CH3:10])([CH3:9])[CH3:8]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86648397(2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(2-methoxycarbonyl-ethyl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 59614423(2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(3-hydroxy-propyl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 74.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

1.0M solution of LAH (1.7 ml, 1.7 mmol) in diethylether solution is added to (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(2-methoxycarbonyl-ethyl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (350 mg, 0.58 mmol) in diethylether (8 ml) at 0° C., and this mixture is stirred for 0.5 hour at the same temperature. The reaction mixture is quenched with saturated ammonium chloride solution. The product is extracted three times with EtOAc. The combined organic layer is washed with 1N HCl, sat NaHCO3 aq. and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc) to give (2R,4S)-4-{(3,5-bis-trifluoromethyl-benzyl)-[5-(3-hydroxy-propyl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.25 g, 74%).

Workup

  1. customThe reaction mixture is quenched with saturated ammonium chloride solution
  2. extractionThe product is extracted three times with EtOAc
  3. washThe combined organic layer is washed with 1N HCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by column chromatography on silica gel (eluent: n-hexane/EtOAc)

Sources & evidence

ORD record
ord-0afdc1094dbe446fb2dd82a97eb4cda9
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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