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

HRID 750380Notes

Reaction equation

HRID 750380 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)pentylcarbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

(2S)-6-{[(benzyloxy)carbonyl]amino}-2-[(tert-butoxycarbonyl)amino]-1-({[(1R)-1-phenylethyl]amino}carbonyl)hexyl benzoate (28.0 g, 45.0 mmol) was dissolved in dioxane (200 mL), and a solution of lithium hydroxide (2.47 g, 174 mmol) in water (100 mL) was added. The resulting mixture was stirred for 24 h at room temperature. It was then diluted with ethyl acetate (500 mL), and washed with 1N hydrochloric acid (300 mL). The aqueous 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 aliqouts of saturated aqueous sodium bicarbonate, followed by saturated aqueous sodium chloride (100 mL), and dried over magnesium sulfate. Volatiles were then removed under vacuum to afford 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 (25.61 g, quantitative crude yield). 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 1N hydrochloric acid (300 mL)
  2. extractionThe aqueous layer was back-extracted with two 100 mL portions of ethyl acetate
  3. washwashed with three 200 mL aliqouts of saturated aqueous sodium bicarbonate
  4. dry with materialdried over magnesium sulfate
  5. customVolatiles were then removed under vacuum
  6. customto afford

Sources & evidence

ORD record
ord-8cfc46d0cb614203bf3e59afbadd02b8
Source dataset
uspto-grants-2008_07
Patent number
US07402606B2

Reaction notes

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