512776-95-3 → Bicalutamide

HRID 457266

반응식

HRID 457266 반응식
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C@:12]2([CH3:15])[CH2:14][O:13]2)=[O:11])=[CH:5][C:4]=1[C:16]([F:19])([F:18])[F:17])#[N:2].[Na].[F:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([O-:30])=[O:29])=[CH:24][CH:23]=1>C(Cl)(Cl)Cl.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:15][C:12]([OH:13])([C:10]([NH:9][C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:16]([F:19])([F:18])[F:17])[CH:5]=1)=[O:11])[CH2:14][S:28]([C:25]1[CH:24]=[CH:23][C:22]([F:21])=[CH:27][CH:26]=1)(=[O:30])=[O:29]

참가 물질

6

반응물 2

HCID 23525848512776-95-3HCID 131724648CID 131724648

생성물 1

HCID 2375Bicalutamide

시약·촉매·용매 3

HCID 74236Tetrabutylammonium Bromide촉매HCID 962Water용매HCID 6212Chloroform용매2회

실험 절차

180 mg of the chiral epoxide of example 17 was dissolved in a mixture of 12 ml chloroform and 12 ml of water. 133 mg of sodium-p-fluorobenzenesulfinate and 107 mg of tetrabutylammonium bromide were added. The reaction mixture was heated till reflux and kept at reflux, while stirring vigorously. The reaction was monitored with HPLC. After 4 days at reflux, the starting epoxide was completely converted. The mixture was cooled to room temperature. 10 ml of chloroform was added. The organic layer was washed with 3×20 ml of water, dried (Na2SO4), filtrated and evaporated to dryness. Residue: 226 mg (brown oil). Purification of the residue by column chromatography (Merck silica gel 60; eluens: heptane/ethyl acetate=1/1) afforded R-enantiomer of bicalutamide as a white/yellow solid material. Purified yield: 122 mg (43%). HPLC: 96.3% purity. HPLC (chiral column): 94.7% e.e. 1H and 13C NMR in agreement with R-bicalutamide

후처리

  1. temperatureThe reaction mixture was heated
  2. temperaturetill reflux
  3. temperatureat reflux
  4. temperatureAfter 4 days at reflux
  5. washThe organic layer was washed with 3×20 ml of water
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltrated
  8. customevaporated to dryness
  9. customPurification of the residue by column chromatography (Merck silica gel 60; eluens: heptane/ethyl acetate=1/1)

출처 및 근거

ORD 기록
ord-004a2c2c0860446e94e375bc7db04884
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07186854B2

연결된 노트

불러오는 중…