Triethylamine → Benzyl 3-(3-(benzyloxy)phenyl)-2-(3-(4-(tert-butoxycarbonylamino)benzyl)ureido)propanoate

HRID 1397875Notes

Reaction equation

HRID 1397875 reaction equation
[NH2:1][CH:2]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:15]=1)[C:3]([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].[C:28]([O:32][C:33]([NH:35][C:36]1[CH:43]=[CH:42][C:39]([CH2:40][NH2:41])=[CH:38][CH:37]=1)=[O:34])([CH3:31])([CH3:30])[CH3:29].C(N(CC)CC)C.C[CH2:52][O:53]C(C)=O>>[CH2:21]([O:20][C:16]1[CH:15]=[C:14]([CH2:13][CH:2]([NH:1][C:52]([NH:41][CH2:40][C:39]2[CH:38]=[CH:37][C:36]([NH:35][C:33]([O:32][C:28]([CH3:31])([CH3:29])[CH3:30])=[O:34])=[CH:43][CH:42]=2)=[O:53])[C:3]([O:5][CH2:6][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[O:4])[CH:19]=[CH:18][CH:17]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl Acetate2×HCID 2794659Tert-butyl N-(4-(aminomethyl)phenyl)carbamateHCID 67257589Benzyl 2-amino-3-(3-(benzyloxy)phenyl)propanoate

Product 1

HCID 68334584Benzyl 3-(3-(benzyloxy)phenyl)-2-(3-(4-(tert-butoxycarbonylamino)benzyl)ureido)propanoateYield 68%

Conditions

Temperature
-10 °C

Procedure

173 (470 mg, 1.3 mmol) was dissolved in AcOEt (30 mL) and trisphosgene (0.33 equivalent, 128 mg) was added while stirring at −10° C. The mixture was allowed to warm to room temperature, then refluxed for 1 h. 4-(tert-butoxycarbonylamino)benzylamine (289 mg, 1 equivalent) and triethylamine (2 equivalent) were added successively and the resulting solution was stirring at room temperature overnight. 100 ml of AcOEt are added. The organic phase are washed with 10% citric acid, saturated NaHCO3 and brine then dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (AcOEt/Hexane 5/5) to afford 174 as white solid (540 mg, 68%). 1H NMR (DMSO): δ 1.61 (s, 9H), 3.02 (m, 2H), 4.24 (s, 2H), 4.60 (m, 1H), 5.22 (s, 4H), 6.38 (d, 1H, J=7.6 Hz), 6.62 (m, 1H), 6.70 (d, 1H, J=8.0 Hz), 6.75 (m, 2H), 7.21 (m, 4H), 7.47 (m, 11H), 9.35 (s, 1H).

Workup

  1. temperatureto warm to room temperature
  2. temperaturerefluxed for 1 h
  3. stirringthe resulting solution was stirring at room temperature overnight
  4. washThe organic phase are washed with 10% citric acid, saturated NaHCO3 and brine
  5. dry with materialthen dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (AcOEt/Hexane 5/5)

Sources & evidence

ORD record
ord-05217b4d706547509ae3661efcef5350
Source dataset
uspto-grants-2014_12
Patent number
US08901295B2

Reaction notes

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