Water → Rofecoxib

HRID 1107880Notes

Reaction equation

HRID 1107880 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 (J. Am. Chem. Soc., 1971, 93, p. 2979), 20 mg of Rh4 (CO)12, 1.5 g of Et3N, 10 mL of THF, and 1 mL of H2O under a 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 r.t. to an initial CO pressure of 100 atm. The reaction is carried out at 100° C. for 5 h. The solution is then diluted with 50 mL of benzene and washed with brine and 1N HCl. The benzene solution is dried over Na2SO4, and concentrated. The crude products are separated by column chromatography on silica gel, eluting 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 r.t. to an initial CO pressure of 100 atm
  3. additionThe solution is then diluted with 50 mL of benzene
  4. washwashed with brine and 1N 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. washeluting with 2:1 EtOAc/hexane

Sources & evidence

ORD record
ord-8b94438d8fc74fefb34c6557ebdf8485
Source dataset
uspto-grants-2000_05
Patent number
US06063811

Reaction notes

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