Methyl chloroformate → HCID 57736523, compound

HRID 1641730Notes

Reaction equation

HRID 1641730 reaction equation
[C:1]([O:5][C:6](=[O:39])[NH:7][CH2:8][CH2:9][NH:10][C:11]([C:13]1[CH:18]=[C:17]([CH3:19])[C:16]([CH:20]([C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=2[F:38])[S:21]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)(=[O:23])=[O:22])=[CH:15][N:14]=1)=[O:12])(C)(C)C.ClC(OC)=O.C(N(CC)CC)C>C(Cl)Cl.FC(F)(F)C(O)=O>[CH3:1][O:5][C:6](=[O:39])[NH:7][CH2:8][CH2:9][NH:10][C:11]([C:13]1[CH:18]=[C:17]([CH3:19])[C:16]([CH:20]([C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=2[F:38])[S:21]([C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)(=[O:23])=[O:22])=[CH:15][N:14]=1)=[O:12]

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 57736512HCID 57736512, compound

Product 1

HCID 57736523HCID 57736523, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of tert-butyl[2-[[[5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]meth yl]-4-methylpyridin-2-yl]carbonyl]amino]ethyl]carbamate (90 mg, 0.160 mmol) obtained in Example 82 in methylene chloride (5 ml), trifluoroacetic acid (2 ml) was added, and the mixture was stirred for 3 hours at room temperature. The reaction solution was concentrated under reduced pressure, and methylene chloride and a 0.5 N aqueous sodium hydroxide were added thereto. The organic layer was separated, subsequently dried over anhydrous sodium sulfate, and filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was dissolved in methylene chloride (5 ml), and methyl chloroformate (19 μl, 0.240 mmol) and triethylamine (26 μl, 0.240 mmol) were added thereto. The reaction solution was stirred for 20 hours at room temperature, and was concentrated under reduced pressure. The resulting concentration residue was subjected to silica gel column chromatography, and the fraction obtained from an elution with 60% ethylacetate/hexane was concentrated under reduced pressure. Ethyl acetate-hexane was added to the resulting concentration residue, and the solid thus precipitated was collected by filtration, to obtain the title compound (71 mg, 0.136 mmol, 85%) as a white powder.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure, and methylene chloride
  2. additiona 0.5 N aqueous sodium hydroxide were added
  3. customThe organic layer was separated
  4. dry with materialsubsequently dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. concentrationThe resulting concentration residue
  8. dissolutionwas dissolved in methylene chloride (5 ml)
  9. stirringThe reaction solution was stirred for 20 hours at room temperature
  10. concentrationwas concentrated under reduced pressure
  11. concentrationThe resulting concentration residue
  12. customthe fraction obtained from an elution with 60% ethylacetate/hexane
  13. concentrationwas concentrated under reduced pressure
  14. additionEthyl acetate-hexane was added to the resulting concentration residue
  15. customthe solid thus precipitated
  16. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-0c631c6a842842aca5d96507de5f3c9b
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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