Methanol → tert-butyl (2R,3S)-3-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 2055434Notes

Reaction equation

HRID 2055434 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[C@H:9]1[C:14](O)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].B.CSC.CO.[H][H]>C1COCC1>[OH:13][C@H:10]1[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@@H:9]1[CH2:14][OH:15]

Participants

6

Reactant 4

HCID 887MethanolHCID 12423031(Dimethyl sulfide)trihydroboronHCID 14037017(2S,3S)-1-(tert-Butoxycarbonyl)-3-hydroxypyrrolidine-2-carboxylic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 10910976tert-butyl (2R,3S)-3-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylateYield 99.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
15 °C

Procedure

The product from Example 51A (7.73 g, 33.5 mmol) in dry THF (100 mL)-was treated with borane-methyl sulfide complex (10 M in THF, 7.4 mL, 74 mmol) dropwise over 10 minutes. The solution was refluxed for 1 hour, cooled to 10-20° C., and methanol was added cautiously until there was no obvious evolution of hydrogen. The mixture was concentrated under reduced pressure and the white residue was stirred with water (50 mL) for 10 minutes and then extracted with ethyl acetate (3×100 mL). The extracts were combined, washed with brine (2×10 mL), dried (Na2SO4), and concentrated to provide the title compound as a white solid (7.24 g, 99%). MS (DCI/NH3) m/z 218 (M+H)+.

Workup

  1. temperatureThe solution was refluxed for 1 hour
  2. concentrationThe mixture was concentrated under reduced pressure
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. washwashed with brine (2×10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ab033ac2f6e34414a9d34f29484196c0
Source dataset
uspto-grants-2008_02
Patent number
US07332504B2

Reaction notes

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