Methyl chloroformate → HCID 136403684, compound

HRID 494650Notes

Reaction equation

HRID 494650 reaction equation
Cl.[OH:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C@:6]([CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])([C:13]([O:15][CH2:16][C@H:17]2[CH2:21][CH2:20][CH2:19][NH:18]2)=[O:14])[C:5](=[O:27])[C:4]=1[C:28]1[NH:33][C:32]2[CH:34]=[CH:35][C:36]([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[CH:37][C:31]=2[S:30](=[O:44])(=[O:43])[N:29]=1.[CH3:45][O:46][C:47](Cl)=[O:48].C(N(CC)CC)C>ClCCl>[OH:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C@@:6]([C:13]([O:15][CH2:16][C@H:17]2[CH2:21][CH2:20][CH2:19][N:18]2[C:47]([O:46][CH3:45])=[O:48])=[O:14])([CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[C:5](=[O:27])[C:4]=1[C:28]1[NH:33][C:32]2[CH:34]=[CH:35][C:36]([NH:38][S:39]([CH3:42])(=[O:41])=[O:40])=[CH:37][C:31]=2[S:30](=[O:44])(=[O:43])[N:29]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 136397186HCID 136397186, compound

Product 1

HCID 136403684HCID 136403684, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 173 (0.079 mmol) in dry dichloromethane (1 mL) at 0° C. was added methylchloroformate (0.12 mL, 1.55 mmol) and triethylamine (33 μL, 0.24 mmol). The resulting mixture was stirred at rt 3 h and partitioned between H2O (5 mL) and dichloromethane (3× 5 mL). The combined organic layers were dried over Na2SO4, the drying agent was filtered off, and the solvent was removed in vacuo. To a solution of the resulting residue in methanol (1 mL) was added K2CO3, and the resulting mixture was stirred at rt 90 min. The mixture was partitioned between N HCl (5 mL) and ethyl acetate (3× 5 mL), and the combined organic layers were dried over Na2SO4. The crude product was purified by column chromatography on silica gel using 5% methanol in chloroform, and the title compound was obtained as a lt. yellow solid (48 mg, 88%): 1H NMR (300 MHz, DMSO-d6) δ 0.43 (m, 1H), 0.67 (m, J=6.62 Hz, 3H), 0.71 (d, J=6.62 Hz, 3H), 0.89 (m, 2H), 1.33 (m, 1H), 1.45 (m, 3H), 1.67 (m, 1H), 2.10 (m, 1H), 2.40 (m, 1H), 2.70 (m, 1H), 3.02 (s, 3H), 3.74 (m, 1H), 3.93 (m, 1H), 4.13 (m, 1H), 7.16 (m, 1H), 7.49 (m, 5H), 8.12 (m, 1H), 10.01 (s, 1H), 14.54 (br s, 1H); MS (ESI) m/z=689 [M+H].

Workup

  1. custompartitioned between H2O (5 mL) and dichloromethane (3× 5 mL)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationthe drying agent was filtered off
  4. customthe solvent was removed in vacuo
  5. additionTo a solution of the resulting residue in methanol (1 mL) was added K2CO3
  6. stirringthe resulting mixture was stirred at rt 90 min
  7. customThe mixture was partitioned between N HCl (5 mL) and ethyl acetate (3× 5 mL)
  8. dry with materialthe combined organic layers were dried over Na2SO4
  9. customThe crude product was purified by column chromatography on silica gel using 5% methanol in chloroform

Sources & evidence

ORD record
ord-96445e71973c47b8990ceb14632983bd
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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