Ethanethiol → HCID 11495439, compound

HRID 901099Notes

Reaction equation

HRID 901099 reaction equation
[F:1][C:2]1([F:31])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[N:11]([CH3:30])[C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N+:23]([CH:27]([CH3:29])[CH3:28])(C)[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.COS([O-])(=O)=O.[H-].[Li+].C(S)C>CN(C)C=O>[F:31][C:2]1([F:1])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[N:11]([CH3:30])[C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:27]([CH3:28])[CH3:29])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 6343EthanethiolHCID 62714Lithium hydrideHCID 4694097Methyl sulfate(1-)HCID 69284056HCID 69284056, compound

Product 1

HCID 11495439HCID 11495439, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To mixture of 4-[2-(4,4-difluoro-piperidine-1-carbonyl)-1-methyl-1H-indol-5-yloxy]-1-isopropyl-1-methyl-piperidinium as monomethylsulfate salt (120 mg, 0.2 mmol, 1.0 eq.), lithium hydride (5 mg, 0.5 mmol, 2.5 eq.) in N,N-dimethylformamide (0.5 mL) was added ethanethiol (0.05 mL, 0.6 mmol, 2.7 eq.). The reaction mixture was stirred 1 h at 100° C., cooled down to room temperature and partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate then filtered and concentrated in vacuo. The crude mixture was purified by column chromatography on silica eluting with DCM/2N NH3 in methanol 19/1 to yield 89 mg (96%) of the title compound as white foam. MS (m/e): 420.5 (MH+, 100%).

Workup

  1. temperaturecooled down to room temperature
  2. custompartitioned between water and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. filtrationthen filtered
  6. concentrationconcentrated in vacuo
  7. customThe crude mixture was purified by column chromatography on silica eluting with DCM/2N NH3 in methanol 19/1

Sources & evidence

ORD record
ord-bf81b1afeb0e41e8ba89c3130ad6f0c9
Source dataset
uspto-grants-2008_04
Patent number
US07361682B2

Reaction notes

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