Phosgene → HCID 57842704, compound

HRID 735593Notes

Reaction equation

HRID 735593 reaction equation
C(Cl)(Cl)=O.[NH2:5][C:6]1[CH:7]=[C:8]([C@@H:12]([NH:19][C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:9]=[CH:10][CH:11]=1.[C:30]([O-:33])(O)=[O:31].[Na+].[Br:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42][CH2:43]O)=[C:38]([CH3:45])[CH:37]=1.[N-]=C=O.[H-].[Na+].[Cl-].[NH4+]>C1COCC1.O>[CH2:23]([O:22][C:20]([NH:19][C@H:12]([C:8]1[CH:9]=[CH:10][CH:11]=[C:6]([NH:5][C:30]([O:33][CH2:43][CH2:42][C:39]2[CH:40]=[CH:41][C:36]([Br:35])=[CH:37][C:38]=2[CH3:45])=[O:31])[CH:7]=1)[CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[O:21])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

10

Reactant 7

HCID 6371PhosgeneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 105034IsocyanateHCID 516892Sodium BicarbonateHCID 57842670(S)-ethyl 3-(3-aminophenyl)-3-(benzyloxycarbonylamino)propanoateHCID 578428522-(4-Bromo-2-methylphenyl)ethanol

Product 1

HCID 57842704HCID 57842704, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Phosgene (3.5 mmol, 1.75 mL, 20% in toluene) was added to a solution of 34C (600 mg, 1.75 mmol) and NaHCO3 (1.47 g, 17.5 mmol) at 0° C. After stirring for 1 h at rt, the solution was filtered and concentrated in vacuo. 30B (375 mg, 1.75 mmol) in THF (20 mL) was added to the crude isocyanate and the solution was cooled to −45° C. NaH (93 mg) was added in one portion and the mixture was warmed to 0° C. and stirred for 2 h at 0° C. and 15 h at ambient temperature. Ammonium chloride (5 mL, saturated) was added and the reaction mixture was diluted with water and extracted with EtOAc. The organics were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography (0% to 50% EtOAc in hexanes) to yield 34D (578 mg, 57%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.15 (t, J=7.15 Hz, 3 H) 2.32 (s, 3 H) 2.80-2.87 (m, J=6.87, 6.87 Hz, 2 H) 2.93 (t, J=7.15 Hz, 2 H) 4.05 (q, J=7.15 Hz, 2 H) 4.30 (t, J=7.15 Hz, 2 H) 5.02-5.18 (m, 3 H) 6.95-7.09 (m, 2 H) 7.23-7.37 (m, 10 H).

Workup

  1. filtrationthe solution was filtered
  2. concentrationconcentrated in vacuo
  3. temperaturethe solution was cooled to −45° C
  4. temperaturethe mixture was warmed to 0° C.
  5. stirringstirred for 2 h at 0° C. and 15 h at ambient temperature
  6. extractionextracted with EtOAc
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash chromatography (0% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ebc648b8ea664c5b92b74633ea085040
Source dataset
uspto-grants-2009_09
Patent number
US07592331B2

Reaction notes

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