Methanol → 7-Hydroxymethyl-8-methoxy-2-(2-trimethylsilanyl-ethoxymethyl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one

HRID 1037310Notes

Reaction equation

HRID 1037310 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[C:11](=[O:22])[N:12]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[N:13]=[C:7]2[C:6]=1[O:23][CH3:24])=O.CC(C[AlH]CC(C)C)C.CO.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C(Cl)Cl>[OH:2][CH2:3][C:5]1[CH:10]=[CH:9][N:8]2[C:11](=[O:22])[N:12]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:19])([CH3:21])[CH3:20])[N:13]=[C:7]2[C:6]=1[O:23][CH3:24]

Participants

6

Reactant 4

HCID 887MethanolHCID 9357Potassium Sodium TartrateHCID 14487Diisobutylaluminum hydrideHCID 670678768-Methoxy-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid methyl ester

Product 1

HCID 670678957-Hydroxymethyl-8-methoxy-2-(2-trimethylsilanyl-ethoxymethyl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-oneYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-50 °C

Procedure

To a stirred solution of 8-methoxy-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridine-7-carboxylic acid methyl ester (1.51 g, 4.27 mmol) in dry DCM (50 mL), cooled to −78° C., was added 1 M DIBAL in DCM (8.54 mL, 8.54 mmol) over 3 minutes. The reaction mixture was allowed to warm to −50° C. over 45 minutes, followed by cooling to −78° C. and addition of MeOH (5 mL) to quench the reaction. The reaction mixture was allowed to warm to 0° C. and was diluted with DCM. An aqueous solution of Rochelle salt (200 mL, 10% w/v) was added and the mixture was stirred vigorously for 30 minutes. The aqueous phase was isolated and extracted with DCM. The combined organic phases were washed with water, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 50 to 100% EtOAc in cyclohexane) to afford the title compound (1.23 g, 89%) as a pale yellow solid. LCMS (Method A): RT=4.18 min, [M+H]+=326.

Workup

  1. temperatureby cooling to −78° C.
  2. customto quench
  3. customthe reaction
  4. temperatureto warm to 0° C.
  5. customThe aqueous phase was isolated
  6. extractionextracted with DCM
  7. washThe combined organic phases were washed with water
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-72c8fa9b01794e89a112d3fe0000d5de
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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