Ethyl acetate 2-propanol water → (2S,3S)-2-amino-4-(tert-butyldimethylsilyloxy)-3-methylbutanoic acid

HRID 1873877Notes

Reaction equation

HRID 1873877 reaction equation
[H][H].[Si:3]([O:10][CH2:11][C@@H:12]([CH3:44])[C@H:13]([NH:24]C1(C2C=CC=CC=2)C2C=CC=CC=2C2C1=CC=CC=2)[C:14]([O:16]CC1C=CC=CC=1)=[O:15])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].CCOC(C)=O.CC(O)C.O>CCOC(C)=O.C(Cl)Cl.[Pd]>[NH2:24][C@@H:13]([C@H:12]([CH3:44])[CH2:11][O:10][Si:3]([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4])[C:14]([OH:16])=[O:15]

Participants

7

Reactant 3

HCID 22041847Ethyl acetate 2-propanol waterHCID 86618478(2S,3S)-benzyl 4-(tert-butyldimethylsilyloxy)-3-methyl-2-(9-phenyl-9H-fluoren-9-ylamino)butanoateHCID 178418361HCID 178418361, compound

Product 1

HCID 86618477(2S,3S)-2-amino-4-(tert-butyldimethylsilyloxy)-3-methylbutanoic acid

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A balloon of hydrogen was attached to a mixture of (2S,3S)-benzyl 4-(tert-butyldimethylsilyloxy)-3-methyl-2-(9-phenyl-9H-fluoren-9-ylamino)butanoate (836 mg, 1.447 mmol) and 10% Pd/C (213 mg) in EtOAc (16 mL) and the mixture was stirred at room temperature for ˜21 hr, where the balloon was recharged with H2 as necessary. The reaction mixture was diluted with CH2Cl2 and filtered through a pad of diatomaceous earth (Celite-545), and the pad was washed with EtOAc (200 mL), EtOAc/MeOH (1:1 mixture, 200 mL) and MeOH (750 mL). The combined organic phase was concentrated, and a silica gel mesh was prepared from the resulting crude material and submitted to a flash chromatography (8:2:1 mixture of EtOAc/i-PrOH/H2O) to afford (2S,3S)-2-amino-4-(tert-butyldimethylsilyloxy)-3-methylbutanoic acid as a white fluffy solid (325 mg). (2S,3R)-benzyl 4-(tert-butyldimethylsilyloxy)-3-methyl-2-(9-phenyl-9H-fluoren-9-ylamino)butanoate was similarly elaborated to (2S,3R)-2-amino-4-(tert-butyldimethylsilyloxy)-3-methylbutanoic acid. (2S,3S)-amino acid isomer: 1H NMR (Methanol-d4, δ=3.29 ppm, 400 MHz), 3.76 (dd, J=10.5, 5.2, 1H), 3.73 (d, J=3.0, 1H), 3.67 (dd, J=10.5, 7.0, 1H), 2.37 (m, 1H), 0.97 (d, J=7.0, 3H), 0.92 (s, 9H), 0.10 (s, 6H). LC/MS: Anal. Calcd. for [M+H]+ C11H26NO3Si: 248.17. found 248.44. (2S,3R)-amino acid isomer: 1H NMR (Methanol-d4, δ=3.29 ppm, 400 MHz), 3.76-3.75 (m, 2H), 3.60 (d, J=4.1, 1H), 2.16 (m, 1H), 1.06 (d, J=7.3, 3H), 0.91 (s, 9H), 0.09 (s, 6H). Anal. Calcd. for [M+H]+ C11H26NO3Si: 248.17. found 248.44.

Workup

  1. filtrationfiltered through a pad of diatomaceous earth (Celite-545)
  2. washthe pad was washed with EtOAc (200 mL), EtOAc/MeOH (1:1 mixture, 200 mL) and MeOH (750 mL)
  3. concentrationThe combined organic phase was concentrated
  4. customa silica gel mesh was prepared from the resulting crude material

Sources & evidence

ORD record
ord-5d8c4eded0974c2798f4845a8a71750c
Source dataset
uspto-grants-2012_11
Patent number
US08303944B2

Reaction notes

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