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

HRID 588505Notes

Reaction equation

HRID 588505 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 diisobutylaluminium 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-f5f8e139b102483f932dbe840df1845b
Source dataset
uspto-grants-2016_01
Patent number
US09227951B2

Reaction notes

Loading…