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 422172Notes

Reaction equation

HRID 422172 reaction equation
[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

Participants

5

Reactant 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

Product 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-carbonitrileYield 62.5%

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent2×

Procedure

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+).

Workup

  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)

Sources & evidence

ORD record
ord-714646c725fa4ace9121fbdc44b61bd5
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

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