Hydrochloric Acid → Rofecoxib

HRID 964350노트

반응식

HRID 964350 반응식
[C:1]1([CH2:7][C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:12][C:13]([C:15]1[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=1)=O.C(N(CC)CC)C.C1CCN2C(=NCCC2)CC1.Cl>C(#N)C.ClCCl.O>[C:1]1([C:7]2[C:8](=[O:10])[O:9][CH2:12][C:13]=2[C:15]2[CH:16]=[CH:17][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:19][CH:20]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 999Phenylacetic AcidHCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 7358232-Bromo-4'-(methylsulfonyl)acetophenone

생성물 1

HCID 5090Rofecoxib

시약·촉매·용매 3

HCID 962Water용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

실험 절차

To a solution of phenylacetic acid (27.4 g, 201 mmol) and 2-bromo-1-(4-(methylsulfonyl)phenyl)ethanone (Example 9, Step 1) (60 g, 216 mmol, 1.075 eq.) in acetonitrile (630 mL) at 25° C. was added slowly triethylamine (30.8 mL, 1.1 eq.). The mixture was stirred for 20 min. at room temperature and then cooled in an ice bath. DBU (60.1 mL, 3 eq.) was slowly added. After stirring for 20 min. in the ice bath, the reaction was complete and the mixture was acidified with 1N HCl (color changes from dark brown to yellow). Then 2.4 L of ice and water were added, stirred for a few minutes, then the precipitate was filtered and rinsed with water (giving 64 g of crude wet product). The solid was dissolved in 750 mL of dichloromethane (dried over MgSO4, filtered) and 300 g of silica gel was added. The solvent was evaporated to near dryness (silica gel a bit sticky) and the residue was applied on top of a silica gel plug (sintered glass funnel) eluted with 10% EtOAc/CH2 Cl2, giving after evaporation of the solvent and swish in ethyl acetate, 36.6 g (58%) of the title compound.

후처리

  1. temperaturecooled in an ice bath
  2. stirringstirred for a few minutes
  3. filtrationthe precipitate was filtered
  4. washrinsed with water (
  5. customgiving 64 g of crude wet product)
  6. addition300 g of silica gel was added
  7. customThe solvent was evaporated to near dryness (silica gel a bit sticky) and the residue
  8. washeluted with 10% EtOAc/CH2 Cl2
  9. customgiving
  10. customafter evaporation of the solvent

출처 및 근거

ORD 기록
ord-16972b4f054244df90426d2bf5998e56
출처 데이터셋
uspto-grants-1998_06
특허 번호
US05767291

반응 노트

불러오는 중…