Rofecoxib → (2Z)-2-[4-(methylsulfonyl)phenyl]-3-phenylbut-2-ene-1,4-diol

HRID 1375702

Reaction equation

HRID 1375702 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH2:15][O:14][C:13](=[O:16])[C:12]=2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].CC(C[AlH]CC(C)C)C.[OH-].[Na+]>ClCCl>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8](/[C:11](=[C:12](\[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)/[CH2:13][OH:16])/[CH2:15][OH:14])=[CH:9][CH:10]=1)(=[O:3])=[O:4]

Participants

5

Reactant 3

HCID 5090RofecoxibHCID 14487Diisobutylaluminum hydrideHCID 14798Sodium Hydroxide

Product 1

HCID 57434773(2Z)-2-[4-(methylsulfonyl)phenyl]-3-phenylbut-2-ene-1,4-diolYield 98.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 110 g of 4-(4-methanesulfonyl-phenyl)-3-phenyl-5H-furan-2-one in 1.5 L of dichloromethane stirred at −78° C., 150 mL of DIBAL was added dropwise. The resulting mixture was warmed to room temperature and stirred overnight. The reaction mixture was then cooled to −78° C., and 1.2 L of 1 M aqueous NaOH was added dropwise. After the addition, the resulting mixture was warmed to room temperature and the organic phase was separated. The aqueous phase was extracted with dichloromethane. The organic phases were combined and dried over Na2SO4. 110 g of the titled compound was obtained after evaporation. 1H NMR (acetone-d6, 500 M Hz): δ 7.69 (d, 2H), 7.36 (d, 2H), 7.16–7.05 (m, 5H), 4.66 (d, 2H), 4.63 (d, 2H), 4.19 (t, 1H, OH), 4.17 (t, 1 H. OH), 3.04 (s, 3H).

Workup

  1. temperatureThe reaction mixture was then cooled to −78° C.
  2. additionAfter the addition
  3. temperaturethe resulting mixture was warmed to room temperature
  4. customthe organic phase was separated
  5. extractionThe aqueous phase was extracted with dichloromethane
  6. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-5edd1a315fdf4ebbb46c36c2676df4c7
Source dataset
uspto-grants-2007_01
Patent number
US07169809B2

Linked notes

Loading…