Diisobutylaluminum hydride → (3-{1-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3 dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylphenyl)methanol

HRID 515238Notes

Reaction equation

HRID 515238 reaction equation
[F:1][C:2]1([F:29])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([C:15]3[CH:16]=[C:17]([CH:22]=[CH:23][C:24]=3[CH3:25])[C:18](OC)=[O:19])=[CH:12][CH:13]=2)[N:8]([CH3:26])[S:7]1(=[O:28])=[O:27].CC(C[AlH]CC(C)C)C>C1COCC1>[F:29][C:2]1([F:1])[CH2:4][CH:3]1[CH2:5][N:6]1[C:14]2[C:9](=[N:10][C:11]([C:15]3[CH:16]=[C:17]([CH2:18][OH:19])[CH:22]=[CH:23][C:24]=3[CH3:25])=[CH:12][CH:13]=2)[N:8]([CH3:26])[S:7]1(=[O:27])=[O:28]

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 67411535Methyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzoate

Product 1

HCID 67409954(3-{1-[(2,2-Difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3 dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylphenyl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Methyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzoate (38-1) (8.0 g, 18.9 mmol, 1.0 eq) dissolved in THF (100 mL) and cooled to −78° C. DIBAL-H (60.0 mL, 60.0 mmol, 3.2 eq, 1.0 M in heptane) was added and the mixture was stirred at the same temperature. After 10 minutes the reaction was carefully quenched by an addition of Rochelle's Salt (15 mL) and stirred for 3 hours warming to ambient temperature. The mixture was extracted with EtOAc (300 mL), washed with water (2×50 mL) and brine (50 mL), dried over MgSO4, filtered and concentrated to afford (3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylphenyl)methanol (39-1) as a tan solid. No further purification was necessary. HRMS m/z (M+H) 396.1188 found, 396.1188 required.

Workup

  1. customAfter 10 minutes the reaction was carefully quenched by an addition of Rochelle's Salt (15 mL)
  2. stirringstirred for 3 hours
  3. temperaturewarming to ambient temperature
  4. extractionThe mixture was extracted with EtOAc (300 mL)
  5. washwashed with water (2×50 mL) and brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e57f77b6ccdf4dab82fe6e49ff2d22b4
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

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