Diisobutylaluminum hydride → (1-Benzylindazol-3-yl)methanol

HRID 343095Notes

Reaction equation

HRID 343095 reaction equation
C([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:12]=1)=O)C1C=CC=CC=1.CC(C[AlH]CC(C)C)C>ClCCl.CCCCCC>[CH2:20]([N:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:11]([CH2:9][OH:8])=[N:12]1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

5

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 10712329Benzyl 1-benzyl-1H-indazole-3-carboxylate

Product 1

HCID 10657568(1-Benzylindazol-3-yl)methanolYield 87.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

To a stirring solution of 735 mg (2.15 mmol) of 1-Benzyl-1H-indazole-3-carboxylic acid benzyl ester, prepared as in Intermediate 14, in 15 mL dichloromethane at -78° C. is added dropwise over 5 min a solution of 5.4 mL (5.4 mmol, 2.5 equiv) of a 1.0M solution of DIBAL-H in hexane. The resulting solution is allowed to slowly warm to RT over a 4 h period then quenched by careful addition of 5 mL of H2O. The reaction mixture is poured into 100 mL of EtOAc and extracted with 1N HCl (1×100 mL), dried (MgSO4), and the solvent removed in vacuo. Purification of the crude material by silica gel flash column chromatography using hexane/EtOAc 1/1 as eluent afforded 448 mg of the title compound as a pale yellow solid: 1H NMR (CDCl3, 300 MHz) δ7.80 (d, 1H), 7.40-7.08 (m, 8H), 5.50 (s, 2H), 5.04 (d, 2H), 2.24 (m, 1H); Rf =0.50 in hexane/EtOAc 1/1.

Workup

  1. customthen quenched by careful addition of 5 mL of H2O
  2. additionThe reaction mixture is poured into 100 mL of EtOAc
  3. extractionextracted with 1N HCl (1×100 mL)
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customPurification of the crude material by silica gel flash column chromatography

Sources & evidence

ORD record
ord-d324a64127af45a592a90f878361635e
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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