Dichloromethane → HCID 11764802, compound

HRID 441187Notes

Reaction equation

HRID 441187 reaction equation
[NH2:1][C:2]1[C:3](=[O:35])[N:4]([CH2:14][C:15]([NH:17][CH:18]([CH:32]([CH3:34])[CH3:33])[CH:19]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[C:20]([F:23])([F:22])[F:21])=[O:16])[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.C([N:38]([CH2:41][CH3:42])[CH2:39][CH3:40])C.Cl[C:44](Cl)([O:46][C:47](=[O:53])OC(Cl)(Cl)Cl)Cl.[CH2:55](Cl)Cl>>[Si:25]([O:24][CH:19]([C:20]([F:23])([F:21])[F:22])[CH:18]([NH:17][C:15](=[O:16])[CH2:14][N:4]1[C:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][CH:7]=[C:2]([NH:1][C:47]([O:46][CH2:44][C:55]2[CH:40]=[CH:39][N:38]=[CH:41][CH:42]=2)=[O:53])[C:3]1=[O:35])[CH:32]([CH3:33])[CH3:34])([C:28]([CH3:29])([CH3:30])[CH3:31])([CH3:27])[CH3:26]

Participants

5

Reactant 4

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 94429TriphosgeneHCID 10391657HCID 10391657, compound

Product 1

HCID 11764802HCID 11764802, compound

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(3-amino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)acetamide (1.00 g) in dry methylene chloride (17 mL) was added dry triethylamine (1.91 mL). The resultant solution was cooled to 0° C. and was treated with a solution of triphosgene (288 mg) in methylene chloride (3 mL) over 5 min. The addition syringe was washed with 2 mL fresh methylene chloride which was then added to the reaction mixture. The reaction mixture was stirred at 0° C. for 45 min, at which time 4-pyridylcarbinol (688 mg) was added as a solid. Stirring was continued 1 h at 0° C. then overnight at room temperature. The mixture was diluted with methylene chloride, washed (saturated sodium bicarbonate solution), dried and evaporated to a brown foam. Purification by flash chromatography, eluting with methylene chloride:methanol (50:1) gave N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)-2-[2-oxo-6-phenyl-3-(4-pyridylmethoxycarbonylamino)-1,2-dihydro-1-pyridyl]acetamide as a yellow-brown solid (1.18 g); TLC: Rf =0.36, eluted twice with dichloromethane:methanol (50:1); MS: m/z=647(M+1).

Workup

  1. washThe addition syringe was washed with 2 mL fresh methylene chloride which
  2. additionwas then added to the reaction mixture
  3. additionwas added as a solid
  4. stirringStirring
  5. waitwas continued 1 h at 0° C.
  6. customovernight
  7. customat room temperature
  8. additionThe mixture was diluted with methylene chloride
  9. washwashed (saturated sodium bicarbonate solution)
  10. customdried
  11. customevaporated to a brown foam
  12. customPurification by flash chromatography
  13. washeluting with methylene chloride:methanol (50:1)

Sources & evidence

ORD record
ord-62ad78de9867486cb286d60cbed08e60
Source dataset
uspto-grants-1996_05
Patent number
US05521179

Reaction notes

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