Boc-D-alanine methyl ester → tert-butyl N-((2R)-1-oxopropan-2-yl)carbamate

HRID 1037966Notes

Reaction equation

HRID 1037966 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:14])[C:10](OC)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C>C(Cl)Cl>[O:11]=[CH:10][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH3:14]

Participants

4

Reactant 2

HCID 637612Boc-D-alanine methyl esterHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 10910049tert-butyl N-((2R)-1-oxopropan-2-yl)carbamateYield 165%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled solution of (R)-methyl 2-(tert-butoxycarbonylamino)propanoate (40.0 g, 98.0 mmol) in DCM (200 mL) at −78° C. was added diisobutylaluminum hydride (208 mL, 1.0 M in THF) dropwise over 30 min. The reaction mixture was stirred at −78° C. for 1.5 h then quenched with water (50 mL). After warmed to rt, the white precipitate was removed by filtration over Celite. The organic layer was then washed with brine, dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography (petroleum ether:EtOAc, 10:1) to give (R)-tert-butyl 1-oxopropan-2-ylcarbamate (28.0 g, 82%). 1H NMR (DMSO-d6, 400 MHz) δ 9.43 (s, 1H), 7.33 (d, J=6.0 Hz, 1H), 3.85 (m, 1H), 1.39 (s, 9H), 1.12 (d, J=7.2 Hz, 3H).

Workup

  1. customthen quenched with water (50 mL)
  2. temperatureAfter warmed to rt
  3. customthe white precipitate was removed by filtration over Celite
  4. washThe organic layer was then washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography (petroleum ether:EtOAc, 10:1)

Sources & evidence

ORD record
ord-9cbc93299a524e0fad20be198954d31d
Source dataset
uspto-grants-2013_10
Patent number
US08546588B2

Reaction notes

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