Chloroacetaldehyde → HCID 59916490, compound

HRID 993143Notes

Reaction equation

HRID 993143 reaction equation
[C:1]([NH:5][C:6]([C@@H:8]1[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][N:9]1[CH2:18][C@@H:19]([OH:43])[C@@H:20]([NH:28][C:29](=[O:42])[C@H:30]([C:35]([S:38]([CH3:41])(=[O:40])=[O:39])([CH3:37])[CH3:36])[NH:31][C:32](=[S:34])[NH2:33])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:45][CH:46]=O>C(O)C>[C:1]([NH:5][C:6]([C@@H:8]1[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][N:9]1[CH2:18][C@@H:19]([OH:43])[C@@H:20]([NH:28][C:29](=[O:42])[C@H:30]([C:35]([S:38]([CH3:41])(=[O:40])=[O:39])([CH3:37])[CH3:36])[NH:31][C:32]1[S:34][CH:45]=[CH:46][N:33]=1)[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 33ChloroacetaldehydeHCID 86758584HCID 86758584, compound

Product 1

HCID 59916490HCID 59916490, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirred solution of 255 mg (0.4 mmol) of N-tert-butyl-1,2,3,4,4a(S),5,6,7,8,8a(S)-decahydro-2-[2(R)-hydroxy-3(S)-[[3-(methanesulfonyl)-N-(thiocarbamoyl)-L-valyl]amino]-4-phenylbutyl]-3(S)-isoquinolinecarboxamide in 5 ml of ethanol was treated with 0.1 ml of chloroacetaldehyde (50% solution in water) and heated at reflux for 4 hours. The volatiles were evaporated and the residue partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate. The aqueous phase was extracted with dichloromethane and the combined organic phase was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure to give a solid which was chromatographed on silica eluting with dichloromethane/methanol (19:1) to give 100 mg (38%) of N-tert-butyl-1,2,3,4,4a(S),5,6,7,8,8a(S)-decahydro-2-[2(R)-hydroxy-3(S)-[[3-(methanesulfonyl)-N-(2-thiazolyl)-L-valyl]amino]-4-phenylbutyl]-3(S)-isoquinolinecarboxamide as a white solid, [M+H]+ 662.2.

Workup

  1. temperatureheated
  2. temperatureat reflux for 4 hours
  3. customThe volatiles were evaporated
  4. customthe residue partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate
  5. extractionThe aqueous phase was extracted with dichloromethane
  6. washthe combined organic phase was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. customevaporated under reduced pressure
  9. customto give a solid which
  10. customwas chromatographed on silica eluting with dichloromethane/methanol (19:1)

Sources & evidence

ORD record
ord-e6eeb6ca22b84e68a2851185ce30d68e
Source dataset
uspto-grants-2002_10
Patent number
US06472404B1

Reaction notes

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