Ethanethiol → (3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-1-((S)-1-(ethylthio)butan-2-yl)-3-methylpiperidin-2-one

HRID 1048576노트

반응식

HRID 1048576 반응식
[CH2:1]([C:4]1([CH3:30])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][N:18]=2)[N:6]([C@@H:24]([CH2:27][CH3:28])[CH2:25]O)[C:5]1=[O:29])[CH:2]=[CH2:3].[CH2:31]([SH:33])[CH3:32].C(C=P(CCCC)(CCCC)CCCC)#N>C1C=CC=CC=1.C(Cl)Cl>[CH2:1]([C@@:4]1([CH3:30])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][N:18]=2)[N:6]([C@@H:24]([CH2:27][CH3:28])[CH2:25][S:33][CH2:31][CH3:32])[C:5]1=[O:29])[CH:2]=[CH2:3]

참가 물질

6

반응물 3

HCID 6343EthanethiolHCID 4622928CyanomethylenetributylphosphoraneHCID 58573550(5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one

생성물 1

HCID 58573901(3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-1-((S)-1-(ethylthio)butan-2-yl)-3-methylpiperidin-2-one

시약·촉매·용매 2

HCID 241Benzene용매HCID 6344Dichloromethane용매

반응 조건

온도
100 °C

실험 절차

(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-1-((S)-1-hydroxybutan-2-yl)-3-methylpiperidin-2-one (Example 121, Step L, 100 mg, 0.224 mmol) was azeotroped three times in benzene on a rotary evaporator. The residue was dissolved in toluene and transferred to a reaction vessel. The vessel was flushed with argon. Ethanethiol (33.1 μl, 0.447 mmol) was added followed by cyanomethylenetributylphosphorane (216 μl, 0.894 mmol). The vessel was sealed and the solution was heated to 100° C. for 4 h. The reaction mixture was diluted with DCM (10 ml) and Si-maleimide (Silicycle, 2.1 g; 0.66 mmol/g; 40-63 microns) was added to scavenge excess thiol. After stirring for about 1 h, the mixture was filtered and the silica gel was rinsed with DCM. The filtrate was concentrated on a rotary evaporator. The residue was dissolved in DCM and loaded directly onto a dry 12 g gold-capped Redisep® column (Teledyne Isco, Lincoln, Nebr.). The column was eluted with a gradient of 0 to 5% MeOH:DCM. The fractions containing the desired product were combined and concentrated to afford the title compound as a colorless film.

후처리

  1. customon a rotary evaporator
  2. dissolutionThe residue was dissolved in toluene
  3. customtransferred to a reaction vessel
  4. customThe vessel was flushed with argon
  5. customThe vessel was sealed
  6. additionwas added
  7. filtrationthe mixture was filtered
  8. washthe silica gel was rinsed with DCM
  9. concentrationThe filtrate was concentrated on a rotary evaporator
  10. dissolutionThe residue was dissolved in DCM
  11. customcapped Redisep® column (Teledyne Isco, Lincoln, Nebr.)
  12. washThe column was eluted with a gradient of 0 to 5% MeOH
  13. additionThe fractions containing the desired product
  14. concentrationconcentrated

출처 및 근거

ORD 기록
ord-018c96eb0d9a4cf0a5d18dfa5101f59f
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569341B2

반응 노트

불러오는 중…