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 422172ノート

反応式

HRID 422172 の反応式
[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

参加物

5

反応物 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

生成物 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-carbonitrile収率 62.5%

試薬・触媒・溶媒 1

HCID 12679Hexamethylphosphoramide溶媒2 回

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-714646c725fa4ace9121fbdc44b61bd5
出典データセット
uspto-grants-2012_01
特許番号
US08101605B2

反応ノート

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