Tert-Butylamine → (S)-[2-[(1,1-dimethylethyl)amino]-2-oxo-1-(phenylmethyl)ethyl]-carbamic acid 1,1-dimethylethyl ester

HRID 568082

Reaction equation

HRID 568082 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:25]([OH:27])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14](OCC2C=CC=CC=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[C:61]([NH2:65])([CH3:64])([CH3:63])[CH3:62]>CN(C=O)C.CCOCC>[CH3:4][C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:25]([NH:65][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:27])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6385Tert-ButylamineHCID 81531DiisopropylethylamineHCID 98763O-benzyl-N-((tert-butoxy)carbonyl)-L-tyrosineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 11809380(S)-[2-[(1,1-dimethylethyl)amino]-2-oxo-1-(phenylmethyl)ethyl]-carbamic acid 1,1-dimethylethyl esterYield 153.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-(tert-Butyloxycarbonyl)-O-benzyl-L-tyrosine (Bachem, 2.00 g, 5.38 mmol) in 20 mL of DMF was cooled to 0° C. and treated with i-Pr2NEt (1.5 mL, Aldrich, Milwaukee, Wis.) followed by O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluoro-phosphate (2.04 g, 538 mmol, Novabiochem, La Jolla, Calif.). The resulting suspension was stirred for 30 minutes at 0° C. and then treated with tert-butylamine (0.48 g, 6.56 mmol, Aldrich, Milwaukee, Wis.). The reaction mixture was stirred for 1 hour at 0° C. and warmed to room temperature. The reaction mixture was then poured into Et2O, and washed sequentially with saturated aqueous NaUCO3 solution and saturated aqueous NaCl solution. The organic phase was dried over MgSO4, filtered, and concentrated. The crude residue was purified by chromatography (silica gel, 3:1 heptane/ethyl acetate) to give (S)-[2-[(1,1-dimethylethyl)amino]-2-oxo-1-(phenylmethyl)ethyl]-carbamic acid 1,1-dimethylethyl ester (2.65 g). MS (CI) 427 (MH)+.

Workup

  1. stirringThe reaction mixture was stirred for 1 hour at 0° C.
  2. temperaturewarmed to room temperature
  3. washwashed sequentially with saturated aqueous NaUCO3 solution and saturated aqueous NaCl solution
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by chromatography (silica gel, 3:1 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-eb0983c825334bc9af97ae19d888d2ee
Source dataset
uspto-grants-2001_01
Patent number
US06180677B2

Linked notes

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