tert-butyl N-[(2S)-4-methyl-1-oxopentan-2-yl]carbamate → (1-{[2-(4-Benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethylamino]-methyl}-3-methyl-butyl)-carbamic acid tert-butyl ester

HRID 278880Notes

Reaction equation

HRID 278880 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:14]=O)[CH2:10][CH:11]([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:16][C@@H:17]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[CH:28][CH:27]=1)[C:18]([NH:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH2:14][NH:16][CH:17]([C:18](=[O:19])[NH:20][C:21]([CH3:23])([CH3:22])[CH3:24])[CH2:25][C:26]1[CH:27]=[CH:28][C:29]([O:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[CH:30][CH:31]=1)[CH2:10][CH:11]([CH3:12])[CH3:13])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 104275tert-butyl N-[(2S)-4-methyl-1-oxopentan-2-yl]carbamateHCID 5003444Sodium cyanoborohydrideHCID 15517727(S)-2-amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide

Product 1

HCID 18711794(1-{[2-(4-Benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethylamino]-methyl}-3-methyl-butyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution consisting of 1.00 g (4.64 mmol) N-tert-butoxycarbonyl-L-leucinal and 1.52 g (4.64 mmol) 2-amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide (Example 2, Step C) in 20 mL methanol containing 1% acetic acid was stirred at 25° C. for 20 minutes, at which time a solution of 0.614 g (9.29 mmol) sodium cyanotrihydridoborate (Aldrich, Milwaukee, Wis.) in 12 mL methanol was added and the resulting mixture stirred for 24 hours. The reaction was quenched by the addition of 3 M HCl in 3 mL increments until the vigorous bubbling subsided. The mixture was neutralized with saturated NaHCO3 solution then extracted with three 50 mL portions of ethyl acetate. The combined extracts were washed with 100 mL brine, dried over anhydrous sodium sulphate, and evaporated at reduced pressure to give a clear, colorless oil which was chromatographed on a silica gel column using 30% to 40% ethyl acetate:hexane to give 735 mg (30%) of [S-(R*,S*)]-(1-{[2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethylamino]-methyl}-3-methyl-butyl)-carbamic acid tert-butyl ester as a clear foam.

Workup

  1. additionwas added
  2. customThe reaction was quenched by the addition of 3 M HCl in 3 mL increments until the
  3. customvigorous bubbling
  4. extractionthen extracted with three 50 mL portions of ethyl acetate
  5. washThe combined extracts were washed with 100 mL brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. customevaporated at reduced pressure
  8. customto give a clear, colorless oil which
  9. customwas chromatographed on a silica gel column

Sources & evidence

ORD record
ord-025316e4e0074a74baeb8687a2616504
Source dataset
uspto-grants-2002_03
Patent number
US06362174B1

Reaction notes

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