(3,4-Dichlorophenyl)methanesulfonyl chloride → 17-cyclopropylmethyl-3-tert-butyldimethylsilyloxy-14beta-hydroxy-4,5alpha-epoxy-6alpha-(N-methyl-3,4-dichlorophenylmethanesulfonamido)morphinan

HRID 567433

Reaction equation

HRID 567433 reaction equation
[Si:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[CH2:13][C@H:14]3[N:26]([CH2:27][CH:28]4[CH2:30][CH2:29]4)[CH2:25][CH2:24][C@:20]45[C:21]=2[C:22]=1[O:23][C@H:19]4[C@@H:18]([NH:31][CH3:32])[CH2:17][CH2:16][C@@:15]35[OH:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl:34][C:35]1[CH:36]=[C:37]([CH2:42][S:43](Cl)(=[O:45])=[O:44])[CH:38]=[CH:39][C:40]=1[Cl:41]>N1C=CC=CC=1>[Si:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]2[CH2:13][C@H:14]3[N:26]([CH2:27][CH:28]4[CH2:29][CH2:30]4)[CH2:25][CH2:24][C@:20]45[C:21]=2[C:22]=1[O:23][C@H:19]4[C@@H:18]([N:31]([CH3:32])[S:43]([CH2:42][C:37]1[CH:38]=[CH:39][C:40]([Cl:41])=[C:35]([Cl:34])[CH:36]=1)(=[O:45])=[O:44])[CH2:17][CH2:16][C@@:15]35[OH:33])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 2794622(3,4-Dichlorophenyl)methanesulfonyl chlorideHCID 5380405917-Cyclopropylmethyl-3-tert-butyldimethylsilyloxy-14beta-hydroxy-4,5alpha-epoxy-6alpha-methylaminomorphinan

Product 1

HCID 9122191517-cyclopropylmethyl-3-tert-butyldimethylsilyloxy-14beta-hydroxy-4,5alpha-epoxy-6alpha-(N-methyl-3,4-dichlorophenylmethanesulfonamido)morphinanYield 78.3%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

203.9 mg of 3-tert-butyldimethylsilyloxy-17-cyclopropylmethyl-4,5α-epoxy-14β-hydroxy-6α-methylaminomorphinan 7 obtained in reference example 5 was dissolved in 3 ml of pyridine followed by the addition of 124 mg of 3,4-dichorophenylmethanesufonylchloride and stirring for 30 minutes at room temperature. After concentrating the reaction system, 3 ml of saturated aqueous sodium bicarbonate and 3 ml of chloroform were added to separate layers, after which the aqueous layer was extracted twice with 3 ml of chloroform. After drying with anhydrous sodium sulfate, the organic layer was concentrated to obtain the oily crude product. This was then purified with silica gel column chromatography (30 g benzene/ethyl acetate=5/1) to obtain 235.4 mg of the target compound (yield: 78%).

Workup

  1. concentrationAfter concentrating the reaction system, 3 ml of saturated aqueous sodium bicarbonate and 3 ml of chloroform
  2. additionwere added
  3. customto separate layers
  4. extractionafter which the aqueous layer was extracted twice with 3 ml of chloroform
  5. dry with materialAfter drying with anhydrous sodium sulfate
  6. concentrationthe organic layer was concentrated
  7. customto obtain the oily crude product
  8. customThis was then purified with silica gel column chromatography (30 g benzene/ethyl acetate=5/1)

Sources & evidence

ORD record
ord-0b86d96cb9e841e78af2563a0e2536f8
Source dataset
uspto-grants-2001_01
Patent number
US06177438B1

Linked notes

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