Ethyl chloroformate → HCID 59050113, compound

HRID 1265226Notes

Reaction equation

HRID 1265226 reaction equation
Cl.[CH:2]1([NH:5][C:6]2[C:9](=[O:10])[C:8](=[O:11])[C:7]=2[NH:12][C:13]2[CH:14]=[C:15]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][C@@H:27]([C:29]([O:31][CH3:32])=[O:30])[NH2:28])=[CH:21][CH:20]=3)[CH:16]=[CH:17][CH:18]=2)[CH2:4][CH2:3]1.Cl[C:34]([O:36][CH2:37][CH3:38])=[O:35].C(N(C(C)C)C(C)C)C.[NH4+].[Cl-]>C1COCC1.C(OCC)(=O)C>[CH:2]1([NH:5][C:6]2[C:9](=[O:10])[C:8](=[O:11])[C:7]=2[NH:12][C:13]2[CH:14]=[C:15]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][C@@H:27]([C:29]([O:31][CH3:32])=[O:30])[NH:28][C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:21][CH:20]=3)[CH:16]=[CH:17][CH:18]=2)[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 20575833HCID 20575833, compound

Product 1

HCID 59050113HCID 59050113, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

The compound of Example 15 (97.0 mg, 0.2 mmol, 1 equiv) and ethyl chloroformate (29.8 mg, 0.3 mmol, 1.3 equiv) were suspended in THF (2 mL) and cooled to 0° C. Ethyldiisopropyl amine (82.1 mg, 0.6 mmol, 3 equiv) was added dropwise and the reaction mixture was allowed to reach rt. It was stirred for 1 hour at ambient temperature. Ethyl acetate and saturated aqueous NH4Cl solution were added and the phases were separated. The aqueous layer was extracted three times with ethyl acetate and the combined organic extracts were dried over Na2SO4. After removal of the solvents under reduced pressure the crude product was purified by chromatography (SiO2, gradient CH/EtOAc 6:4 to EtOAc 100%). Yield 39.0 mg, 37.3%. 1H NMR (CDCl3, 400 MHz) δ 7.61-7.55 (m, 1H); 7.52-7.49 (m, 2H); 7.31-7.18 (m, 2H); 7.09-6.96 (m, 1H); 6.82 (d, 2H); 5.71 (d, 1H); 4.79-4.64 (m, 1H); 4.34-4.29 (m, 1H); 4.19-4.02 (m, 4H); 3.75 (s, 3H); 3.19-3.06 (m, 1H); 1.23 (t, 3H); 0.89-0.75 (m, 2 H); 0.76-0.68 (m, 2H). MS (EI) 494 (M+H).

Workup

  1. customto reach rt
  2. customthe phases were separated
  3. extractionThe aqueous layer was extracted three times with ethyl acetate
  4. dry with materialthe combined organic extracts were dried over Na2SO4
  5. customAfter removal of the solvents under reduced pressure the crude product
  6. customwas purified by chromatography (SiO2, gradient CH/EtOAc 6:4 to EtOAc 100%)

Sources & evidence

ORD record
ord-c3191ac9cc394512a54f433ff35d3ae3
Source dataset
uspto-grants-2003_04
Patent number
US06545029B2

Reaction notes

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