4-Methylmorpholine → (2R,5S)-tert-butyl 2-(hydroxymethyl)-5-phenylpyrrolidine-1-carboxylate

HRID 732370Notes

Reaction equation

HRID 732370 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:11][CH2:10][C@@H:9]1[C:19](O)=[O:20])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>COCCOC.O>[C:1]([O:5][C:6]([N:8]1[C@H:12]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:11][CH2:10][C@@H:9]1[CH2:19][OH:20])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 17040153(5S)-1-(tert-Butoxycarbonyl)-5-phenyl-D-proline

Product 1

HCID 68816114(2R,5S)-tert-butyl 2-(hydroxymethyl)-5-phenylpyrrolidine-1-carboxylateYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

To an ice cold solution of commercially available (2R,5S)-5-phenyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (1.00 g, 3.45 mmol) in 1,2-dimethoxyethane (5 mL) is added 4-methylmorpholine (0.4 mL, 3.795 mmol) and isobutyl chloroformate (0.50 mL, 3.795 mmol). Stir 15 min and filter into cold flask. Add sodium borohydride (0.196 g, 5.17 mmol) in water (3 mL), followed by addition of water (50 mL). Extract product with ethyl acetate (3×50 mL) and wash with saturated aqueous sodium chloride, dry (magnesium sulfate) and purify on silica gel to give the title compound (0.886 g, 93%).

Workup

  1. filtrationfilter into cold flask
  2. washExtract product with ethyl acetate (3×50 mL) and wash with saturated aqueous sodium chloride
  3. dry with materialdry (magnesium sulfate)
  4. custompurify on silica gel

Sources & evidence

ORD record
ord-c66594cfc441489289fec32c93fda37d
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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