Propyl mercaptan → (1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acid

HRID 422159Notes

Reaction equation

HRID 422159 reaction equation
[H-].[Li+].C(S)CC.[CH3:7][O:8][C:9]1[CH:26]=[C:25]([C:27]([O-:29])=[O:28])[CH:24]=[C:23]2[C:10]=1[C@H:11]1[C@H:20]([CH2:21][S:22]2(=[O:31])=[O:30])[C@:19]2([CH3:32])[C@H:14]([C:15]([CH3:34])([CH3:33])[CH2:16][CH2:17][CH2:18]2)[CH2:13][CH2:12]1>CN(P(N(C)C)(N(C)C)=O)C>[CH3:7][O:8][C:9]1[CH:26]=[C:25]([C:27]([OH:29])=[O:28])[CH:24]=[C:23]2[C:10]=1[C@H:11]1[C@H:20]([CH2:21][S:22]2(=[O:31])=[O:30])[C@:19]2([CH3:32])[C@H:14]([C:15]([CH3:34])([CH3:33])[CH2:16][CH2:17][CH2:18]2)[CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 7848Propyl mercaptanHCID 62714Lithium hydrideHCID 86654190(1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylate

Product 1

HCID 86654189(1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8lambda6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acidYield 95%

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent2×

Procedure

A mixture of lithium hydride (0.66 g, 83 mmol) and n-propanethiol (8.7 mL, 99 mmol) in HMPA (20 mL) was stirred at room temperature for 30 min under N2. To the mixture (1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylate (59) (3.6 g, 8.3 mmol) in HMPA (10 mL) was added. The mixture was heated at 130° C. for 1 h. The mixture was cooled to room temperature and quenched with 1 M HCl, then extracted with EtOAc. The organic layer was concentrated to dryness. The residue was purified by flash chromatography on silica gel (CH2Cl2/MeOH, 10:1) to yield (1R,10S,11S,16S)-3-methoxy-11,15,15-trimethyl-8,8-dioxo-8λ6-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene-5-carboxylic acid (61) (3.2 g, 95% yield) as a white solid. 1H NMR (CD3OD): δ 7.91 (d, 1H), 7.54 (d, 1H), 3.59 (m, 1H), 3.38 (m, 2H), 2.24 (m, 1H), 1.86 (m, 8H), 1.36-1.16 (m, 3H), 1.09-1.03 (m, 2H), 1.02 (s, 3H), 0.89 (s, 3H), 0.87 (s, 3H). MS m/z 405 (C22H30NO5S−H+).

Workup

  1. temperatureThe mixture was heated at 130° C. for 1 h
  2. temperatureThe mixture was cooled to room temperature
  3. customquenched with 1 M HCl
  4. extractionextracted with EtOAc
  5. concentrationThe organic layer was concentrated to dryness
  6. customThe residue was purified by flash chromatography on silica gel (CH2Cl2/MeOH, 10:1)

Sources & evidence

ORD record
ord-788793d86a7640208fb556344c47b188
Source dataset
uspto-grants-2012_01
Patent number
US08101605B2

Reaction notes

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