Propyl mercaptan → (1R,10R,11S,16S)-5-hydroxy-1,11,15,15-tetramethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carbonitrile

HRID 422172노트

반응식

HRID 422172 반응식
[H-].[Li+].C(S)CC.C[O:8][C:9]1[CH:26]=[C:25]2[C:12]([C@@:13]3([CH3:30])[C@H:22]([CH2:23][S:24]2)[C@:21]2([CH3:27])[C@H:16]([C:17]([CH3:29])([CH3:28])[CH2:18][CH2:19][CH2:20]2)[CH2:15][CH2:14]3)=[C:11]([C:31]#[N:32])[CH:10]=1>CN(P(N(C)C)(N(C)C)=O)C>[OH:8][C:9]1[CH:26]=[C:25]2[C:12]([C@@:13]3([CH3:30])[C@H:22]([CH2:23][S:24]2)[C@:21]2([CH3:27])[C@H:16]([C:17]([CH3:28])([CH3:29])[CH2:18][CH2:19][CH2:20]2)[CH2:15][CH2:14]3)=[C:11]([C:31]#[N:32])[CH:10]=1

참가 물질

5

반응물 3

HCID 7848Propyl mercaptanHCID 62714Lithium hydrideHCID 58294810(1R,10R,11S,16S)-5-methoxy-1,11,15,15-tetramethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carbonitrile

생성물 1

HCID 53240751(1R,10R,11S,16S)-5-hydroxy-1,11,15,15-tetramethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carbonitrile수율 62.5%

시약·촉매·용매 1

HCID 12679Hexamethylphosphoramide용매2회

실험 절차

A mixture of LiH (0.127 g, 16.2 mmol), 1-propyl thiol (1.60 mL, 17.6 mmol) in HMPA (2 mL) was stirred at room temperature for 15 minutes under N2. To the mixture, a solution of (1R,10R,11S,16S)-5-methoxy-1,11,15,15-tetramethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carbonitrile (77) (0.10 g 0.27 mmol) in HMPA (3.0 mL) was added. The mixture was heated at 130° C. for 30 min. The reaction mixture was cooled to room temperature and quenched with water, then extracted with EtOAc. The organic layer was separated and concentrated to dryness. The crude product was purified by flash chromatography on silica gel (Hexanes/EtOAc, 10:1) to yield (1R,10R,11S,16S)-5-hydroxy-1,11,15,15-tetramethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-3-carbonitrile (78) (0.06 g, 62%) as a white solid. 1H NMR (CDCl3): δ 6.86 (d, 1H), 6.72 (d, 1H), 4.72 (s, 1H), 3.47 (m, 1H), 2.86 (m, 2H), 1.86-1.56 (m, 4H), 1.52-1.36 (m, 6H), 1.28-0.97 (m, 3H), 0.94 (s, 3H), 0.90 (m, 1H), 0.87 (s, 3H), 0.84 (s, 3H). MS m/z 354 (C22H29NOS−H+).

후처리

  1. temperatureThe mixture was heated at 130° C. for 30 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with water
  4. extractionextracted with EtOAc
  5. customThe organic layer was separated
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified by flash chromatography on silica gel (Hexanes/EtOAc, 10:1)

출처 및 근거

ORD 기록
ord-714646c725fa4ace9121fbdc44b61bd5
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101605B2

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