Methanol → (S)-2-methyl-N-((1S)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethyl)propane-2-sulfinamide

HRID 475218Notes

Reaction equation

HRID 475218 reaction equation
[CH3:1][C:2]([S@:5]([NH2:7])=[O:6])([CH3:4])[CH3:3].[O:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[N:14]1[C:18]2[CH:19]=[CH:20][C:21]([C:23](=O)[CH3:24])=[CH:22][C:17]=2[N:16]=[CH:15]1.CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].CO>C1COCC1.[Cl-].[Na+].O>[CH3:1][C:2]([S@@:5]([NH:7][C@H:23]([C:21]1[CH:20]=[CH:19][C:18]2[N:14]([CH:9]3[CH2:10][CH2:11][CH2:12][CH2:13][O:8]3)[CH:15]=[N:16][C:17]=2[CH:22]=1)[CH3:24])=[O:6])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 887MethanolHCID 3611392Lithium tri-s-butylborohydrideHCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 712726001-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethanone

Product 1

HCID 86694727(S)-2-methyl-N-((1S)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethyl)propane-2-sulfinamideYield 50%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of (R)-2-methylpropane-2-sulfinamide (6.9 g, 57.31 mmol) and Ti(OEt)4 (26.1 g, 114.62 mmol) in THF (200 mL) at RT was added 82 (14 g, 57.31 mmol). The reaction mixture was heated to 75° C. overnight. After MS analysis indicated complete conversion of 122, the mixture was cooled to RT and then to −48.0° C. L-Selectride (172 mL, 1M solution in THF) was added dropwise. The reaction mixture was warmed. When the reduction was complete the reaction mixture was cooled to 0° C. and MeOH was added dropwise until gas evolution was no longer observed. The crude reaction mixture was poured into an equal volume of rapidly stirred brine. The resulting suspension was filtered through a plug of Celite® and the filter cake was washed with EtOAc. The filtrate was washed with brine, and the brine layer was extracted with EtOAc, dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by SiO2 chromatography eluting with DCM/MeOH (20:1) to afford 10 g (50%) of (S)-2-methyl-N-((1S)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethyl)propane-2-sulfinamide (124) as yellow oil.

Workup

  1. temperaturethe mixture was cooled to RT
  2. customto −48.0° C
  3. temperatureThe reaction mixture was warmed
  4. temperaturewas cooled to 0° C.
  5. customThe crude reaction mixture
  6. filtrationThe resulting suspension was filtered through a plug of Celite®
  7. washthe filter cake was washed with EtOAc
  8. washThe filtrate was washed with brine
  9. extractionthe brine layer was extracted with EtOAc
  10. dry with materialdried (Na2SO4)
  11. customevaporated under reduced pressure
  12. customThe residue was purified by SiO2 chromatography
  13. washeluting with DCM/MeOH (20:1)

Sources & evidence

ORD record
ord-c3994c0de7b9402d9fc89c828c6fd3a0
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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