Acetic Anhydride → (R)-ethyl 5-acetamido-2-(3-(4-(tert-butoxycarbonylamino)benzyl)ureido)pentanoate

HRID 1397883Notes

Reaction equation

HRID 1397883 reaction equation
C([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][C@@H:15]([NH:21][C:22]([NH:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:28][CH:27]=1)=[O:23])[C:16]([O:18][CH2:19][CH3:20])=[O:17])=O)C1C=CC=CC=1.[C:40](OC(=O)C)(=O)C>CO.[Pd]>[C:9]([NH:11][CH2:12][CH2:13][CH2:14][C@@H:15]([NH:21][C:22]([NH:24][CH2:25][C:26]1[CH:27]=[CH:28][C:29]([NH:32][C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34])=[CH:30][CH:31]=1)=[O:23])[C:16]([O:18][CH2:19][CH3:20])=[O:17])(=[O:8])[CH3:40]

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 86723917(R)-ethyl 5-(benzyloxycarbonylamino)-2-(3-(4-(tert-butoxycarbonylamino)benzyl)ureido)pentanoate

Product 1

HCID 68334448(R)-ethyl 5-acetamido-2-(3-(4-(tert-butoxycarbonylamino)benzyl)ureido)pentanoateYield 88.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

(R)-ethyl 5-(benzyloxycarbonylamino)-2-(3-(4-(tert-butoxy-carbonylamino)benzyl)ureido)pentanoate (1 equivalent, 115 mg, 0.21 mmol) was dissolved in 50 ml of MeOH. The Pd/C (12 mg) and the acetic anhydride (3 equivalent, 60 μl, 0.63 mmol). The reaction mixture was stirred under hydrogen at room temperature for 4 h. Then the mixture was filtrated on celite and the filter was concentrated. the crude was washed by 30 ml NaHCO3 and extracted by 3×30 ml EtOAc. The organic phase was dried over Na2SO4, filtered and concentrated. The crude was purified by flash chromatography (CH2Cl2/MeOH) to afford the amide (84 mg, 78%) a colourless oil Rf=0.27 (CH2Cl2/MeOH 95/5). 1H NMR (200 MHz, CDCl3): δ 7.30 (d, J=8.6 Hz, 2H), 7.18 (d, J=8.6 Hz, 2H), 6.63 (broad s, 1H), 6.28-6.10 (m, 1H), 5.45 (d, J=7.6 Hz, 1H), 5.34-5.20 (m, 1H), 4.52-4.35 (m, 1H), 4.29 (d, J=5.8 Hz 2H), 4.15 (q, J=7.1 Hz, 2H), 3.32-3.12 (m, 2H), 1.94 (s, 3H), 1.90-1.36 (m, 4H) 1.50 (s, 9H), 1.25 (1, J=7.5 Hz, 3H).

Workup

  1. filtrationThen the mixture was filtrated on celite
  2. concentrationthe filter was concentrated
  3. washthe crude was washed by 30 ml NaHCO3
  4. extractionextracted by 3×30 ml EtOAc
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified by flash chromatography (CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-edfe8abf5b0943eab17034457c0d1305
Source dataset
uspto-grants-2014_12
Patent number
US08901295B2

Reaction notes

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