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

HRID 475218ノート

反応式

HRID 475218 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
75 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-c3994c0de7b9402d9fc89c828c6fd3a0
出典データセット
uspto-grants-2014_01
特許番号
US08637537B2

反応ノート

読み込み中…