Lithium Hydroxide → tert-butyl(1S)-5-{[(benzyloxy)carbonyl]amino}-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

HRID 1180743Notes

Reaction equation

HRID 1180743 reaction equation
C([O:9][CH:10]([C:35]([NH:37][C@@H:38]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[CH3:39])=[O:36])[C@@H:11]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:12][CH2:13][CH2:14][CH2:15][NH:16][C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])(=O)C1C=CC=CC=1.[OH-].[Li+]>O1CCOCC1.O.C(OCC)(=O)C>[CH2:20]([O:19][C:17]([NH:16][CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]([NH:27][C:28](=[O:29])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:10]([OH:9])[C:35](=[O:36])[NH:37][C@@H:38]([C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)[CH3:39])=[O:18])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 58979676(2S)-6-{[(Benzyloxy)carbonyl]amino}-2-[(tert-butoxycarbonyl)amino]-1-({[(1R)-1-phenylethyl]amino}carbonyl)hexyl benzoate

Product 1

HCID 58979678tert-butyl(1S)-5-{[(benzyloxy)carbonyl]amino}-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamateYield 110.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

28.0 g (45.0 mmol) of (2S)-6-{[(Benzyloxy)carbonyl]amino}-2-[(tert-butoxycarbonyl)amino]-1-({[(1R)-1-phenylethyl]amino}carbonyl)hexyl benzoate was dissolved in 200 mL of dioxane, and a solution of 2.47 g (174 mmol) of lithium hydroxide in 100 mL of water was added. The resulting mixture was stirred for 24 h at room temperature. It was then diluted with 500 mL of ethyl acetate, and washed with 300 mL of 1N hydrochloric acid. The aqeous layer was back-extracted with two 100 mL portions of ethyl acetate. The extracts were then combined with the original ethyl acetate layer, washed with three 200 mL aliquots of saturated aqueous sodium bicarbonate, followed by 100 mL of saturated aqueous sodium chloride, and dried over magnesium sulfate. Volatiles were then removed under vacuum to afford 25.61 g (quantitative crude yield) of tert-butyl (1S)-5-{[(benzyloxy)carbonyl]amino}-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate as a waxy light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 7.98-7.88 (m, 1H); 7.68-7.63 (m) and 7.49-7.42 (m) total 1H; 7.35-7.10 (m, 10H); 6.31 (d, J=9 Hz) and 6.02 (d, J=9 Hz) total 1H; 5.62-5.53 (br s) and 5.53-5.42 (br s) total 1H; 4.94 (s, 2H), 4.91-4.83 (m, 1H); 3.87 (br s) and 3.79 (br s) total 1H; 3.72-3.58 (m, 1H); 2.99-2.76 (m, 2H); 1.47-1.10 (m, 18H). ES-LCMS m/z 514 (M+H).

Workup

  1. washwashed with 300 mL of 1N hydrochloric acid
  2. extractionThe aqeous layer was back-extracted with two 100 mL portions of ethyl acetate
  3. washwashed with three 200 mL aliquots of saturated aqueous sodium bicarbonate
  4. dry with materialdried over magnesium sulfate
  5. customVolatiles were then removed under vacuum

Sources & evidence

ORD record
ord-84cc60f14441409ab5c3b609e1cba038
Source dataset
uspto-grants-2007_10
Patent number
US07282512B2

Reaction notes

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