tert-Butyl mercaptan → HCID 86731819, compound

HRID 1846970Notes

Reaction equation

HRID 1846970 reaction equation
[CH3:1][C:2]([SH:5])([CH3:4])[CH3:3].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].CC1C=CC(S([O-])(=O)=O)=CC=1.[CH2:27]([C@@:30]1([CH3:56])[CH2:35][C@H:34]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=2)[C@@H:33]([C:43]2[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=2)[N+:32]2[C@@H:50]([CH:53]3[CH2:55][CH2:54]3)[CH2:51][O:52][C:31]1=2)[CH:28]=[CH2:29]>O1CCCC1.O>[CH2:27]([C@@:30]1([CH3:56])[CH2:35][C@H:34]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=2)[C@@H:33]([C:43]2[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=2)[N:32]([C@@H:50]([CH:53]2[CH2:55][CH2:54]2)[CH2:51][S:5][C:2]([CH3:4])([CH3:3])[CH3:1])[C:31]1=[O:52])[CH:28]=[CH2:29]

Participants

6

Reactant 3

HCID 6387tert-Butyl mercaptanHCID 2733832Lithium HexamethyldisilazideHCID 86731820HCID 86731820, compound

Product 1

HCID 86731819HCID 86731819, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

2-Methyl-2-propanethiol (0.195 mL, 1.796 mmol, dried over activated 4 Å molecular sieves) was added to a solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1.0 M, 1.8 mL, 1.8 mmol) in anhydrous tetrahydrofuran (4 mL) at room temperature. The reaction mixture was heated at 60° C. After 15 minutes at 60° C., (3S,5S,6R,8S)-8-allyl-6-(3-chlorophenyl)-5-(4-chlorophenyl)-3-cyclopropyl-8-methyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-α]pyridin-4-ium 4-methylbenzenesulfonate (1.00 g, 1.632 mmol, Example 1, Step F) was added as a solid. The reaction mixture was heated at 60° C. for 12 hours and then cooled to room temperature and diluted with water. The solution was extracted with ethyl acetate thrice and the organics were pooled, washed with brine, dried over sodium sulfate, decanted and concentrated under a vacuum to provide a brown oil. Purification by flash chromatography (80 g SiO2 column, gradient elution of 10 to 60% ethyl acetate in hexanes provided the desired product as a colorless syrup.

Workup

  1. temperatureThe reaction mixture was heated at 60° C. for 12 hours
  2. temperaturecooled to room temperature
  3. extractionThe solution was extracted with ethyl acetate thrice
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. customdecanted
  7. concentrationconcentrated under a vacuum
  8. customto provide a brown oil
  9. customPurification by flash chromatography (
  10. wash80 g SiO2 column, gradient elution of 10 to 60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f3d041e28f5a4feb9fc58c17c7d11a2b
Source dataset
uspto-grants-2015_02
Patent number
US08952036B2

Reaction notes

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