Methyl Isocyanate → tert-butyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-{[(methylamino)carbonyl]amino}pentylcarbamate

HRID 750382Notes

Reaction equation

HRID 750382 reaction equation
[CH3:1][N:2]=[C:3]=[O:4].[NH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C@H:10]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH:11]([OH:23])[C:12](=[O:22])[NH:13][C@@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15]>O1CCCC1>[OH:23][CH:11]([C@@H:10]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:9][CH2:8][CH2:7][CH2:6][NH:5][C:3]([NH:2][CH3:1])=[O:4])[C:12](=[O:22])[NH:13][C@@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15]

Participants

4

Reactant 2

HCID 12228Methyl IsocyanateHCID 58979670tert-butyl (1S)-5-amino-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

Product 1

HCID 58979672tert-butyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-{[(methylamino)carbonyl]amino}pentylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Methylisocyanate (0.472 mL, 8.00 mmol) was added to a slurry of tert-butyl (1S)-5-amino-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate (3.03 g, 8.00 mmol) at 0° C. in anhydrous tetrahydrofuran (60 mL) under nitrogen. The mixture was stirred at 0° C. for 1 h, during which time all solids dissolved. The cold bath was then removed, and the solution was stirred overnight. Volatiles were removed under vacuum, and the resulting foam was further purified by column chromatography on silica gel. Elution with a gradient from 50% to 75% acetone in hexane afforded tert-butyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-{[(methylamino)carbonyl]amino}pentylcarbamate as a white solid after drying under vacuum (3.00 g, 86%). 1H NMR (300 MHz, DMSO-d6) δ 8.06-8.01 (m, 1H); 7.38-7.18 (m, 5H); 6.40 (d, J=10 Hz) and 6.08 (d, J=9 Hz) total 1H, 5.86-5.75 (m, 1H); 5.71-5.51 (m, 2H); 5.01-4.91 (m, 1H); 3.94 (br s) and 3.87 (br s) total 1H, 3.79-3.64 (m, 1H); 3.01-2.81 (m, 2H); 2.54 (d, J=5 Hz, 3H); 1.52-1.16 (m, 18H). ES-LCMS m/z 437 (M+H).

Workup

  1. dissolutiondissolved
  2. customThe cold bath was then removed
  3. stirringthe solution was stirred overnight
  4. customVolatiles were removed under vacuum
  5. customthe resulting foam was further purified by column chromatography on silica gel
  6. washElution with a gradient from 50% to 75% acetone in hexane

Sources & evidence

ORD record
ord-aea43eedd7884cc2b4b5369784c78b80
Source dataset
uspto-grants-2008_07
Patent number
US07402606B2

Reaction notes

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