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

HRID 2403239Notes

Reaction equation

HRID 2403239 reaction equation
[NH2:1][CH:2]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:10]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:23]([O:27][C:28]([NH:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH2:36])=[CH:33][CH:32]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C(N(CC)CC)C.C[CH2:47][O:48]C(C)=O>>[CH2:16]([O:15][C:11]1[CH:10]=[C:9]([CH2:8][CH:2]([NH:1][C:47]([NH:36][CH2:35][C:34]2[CH:33]=[CH:32][C:31]([NH:30][C:28]([O:27][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:29])=[CH:38][CH:37]=2)=[O:48])[C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH:14]=[CH:13][CH:12]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl Acetate2×HCID 2794659Tert-butyl N-(4-(aminomethyl)phenyl)carbamateHCID 4014929Ethyl 2-amino-3-(3-(benzyloxy)phenyl)propanoate

Product 1

HCID 67261903Ethyl 3-(3-(benzyloxy)phenyl)-2-(3-(4-(tert-butoxycarbonylamino)benzyl)ureido)propanoateYield 99%

Conditions

Temperature
-10 °C

Procedure

160 (530 mg, 1.76 mmol) was dissolved in AcOEt (30 mL) and trisphosgene (0.33 equivalent, 173 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 (391 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 161 as white solid (960 mg, 99%). 1H NMR (DMSO): δ 1.28 (t, 3H, J=6.5 Hz), 1.61 (s, 9H), 3.01 (dd, 1H, J=13.8, 8.3 Hz), 3.09 (dd, 1H, J=13.8, 5.0 Hz), 4.19 (q, 2H, J=6.5 Hz), 4.24 (d, 2H, J=5.1 Hz), 4.57 (s, 1H), 5.20 (s, 2H), 6.38 (d, 1H, J=7.8 Hz), 6.61 (t, 1H, J=5.1 Hz), 6.90 (d, 1H, J=7.1 Hz), 7.02 (d, 1H, J=8.7 Hz), 7.21 (d, 2H, J=8.1 Hz), 7.33 (t, 1H, J=7.8 Hz), 7.50 (m, 5H), 7.57 (d, 2H, J=8.1 Hz), 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-00e57284a5ff4d069b9b6ab565b21476
Source dataset
uspto-grants-2014_08
Patent number
US08802666B2

Reaction notes

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