Water → Rofecoxib

HRID 1019189Notes

Reaction equation

HRID 1019189 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:17]#[CH:18])=[CH:7][CH:6]=1)(=[O:4])=[O:3].CCN(CC)CC.C1[CH2:30][O:29][CH2:28]C1.[OH2:31]>>[C:15]1([C:16]2[C:28](=[O:31])[O:29][CH2:30][C:11]=2[C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:10][CH:9]=2)[CH:14]=[CH:13][CH:12]=[CH:17][CH:18]=1

Participants

5

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 184001882-(4-(Methylsulfonyl)phenyl)phenylacetylene

Product 1

HCID 5090Rofecoxib

Procedure

Into a 20 ml glass ampule are added 1 g of 2-(4-(methylsulfonyl)phenyl)phenylacetylene, 20 mg of Rh4(CO)12, 1.5 g of Et3N, 10 ml of THF, 1 ml of water under nitrogen atmosphere, and the ampule is placed in a 100-ml stainless steel autoclave. The reaction system is flushed three times with CO then charged at room temperature to a initial CO pressure of 100 atm. The reaction is carried at 100 iC for 5 h. The solution is then diluted with 50 ml of benzene and washed with brine, iN HCl. The benzene solution is dried over Na2SO4, and concentrated. The crude products are separated by column chromatography on silica gel eluted with 2:1 EtOAc/hexane to give the title compound and its regioisomer.

Workup

  1. customThe reaction system is flushed three times with CO
  2. additionthen charged at room temperature to a initial CO pressure of 100 atm
  3. additionThe solution is then diluted with 50 ml of benzene
  4. washwashed with brine, iN HCl
  5. dry with materialThe benzene solution is dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude products are separated by column chromatography on silica gel
  8. washeluted with 2:1 EtOAc/hexane

Sources & evidence

ORD record
ord-9e519ee93012461183294e9103b419be
Source dataset
uspto-grants-2002_11
Patent number
US06486194B2

Reaction notes

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