1h-Indazole-3-carboxylic acid,4,5,6,7-tetrahydro-1-(phenylmethyl)-,ethyl ester → (4,5,6,7-Tetrahydro-1-benzyl-1H-indazol-3-yl) methanol

HRID 343122Notes

Reaction equation

HRID 343122 reaction equation
C([O:3][C:4]([C:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N:8]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:7]=1)=O)C.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH2:15]([N:8]1[C:9]2[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=2[C:6]([CH2:4][OH:3])=[N:7]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

4

Reactant 2

HCID 105650011h-Indazole-3-carboxylic acid,4,5,6,7-tetrahydro-1-(phenylmethyl)-,ethyl esterHCID 21226445Aluminium lithium hydride

Product 1

HCID 10633931(4,5,6,7-Tetrahydro-1-benzyl-1H-indazol-3-yl) methanolYield 86.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring solution of 1.0 g (3.52 mmol) of 4,5,6,7-Tetrahydro-1-Benzyl-1H-indazole-3-carboxylic acid ethyl ester, prepared as in Part A, in 15 mL of THF at 0° C. is added dropwise over 5 min a solution of 5.3 mL (5.3 mmol, 1.5 equiv) of a 1.0M solution of LiAlH4 in THF. The resulting solution is stirred at RT for 30 min then heated to 50° C. for 1 h. The reaction mixture is cooled to 0° C. and worked up by carefully quenching first with 0.22 mL of H2O, then 0.22 mL of 15% NaOH, then 0.66 mL of H2O. The resulting slurry is filtered and the filter cake triturated with 20 mL EtOAc and refiltered. The filtrates were combined, dried (MgSO4), and the solvent removed in vacuo. Purification of the crude material by Kugelrohr distillation gave 740 mg of (4,5,6,7-Tetrahydro-1-benzyl-1H-indazol-3-yl) methanol as a pale yellow thick oil: bp 225° C. at 0.8 mm; 1H NMR (CDCl3, 300 MHz) δ7.32-7.24 (m, 3H), 7.10 (m, 2H), 5.17 (s, 2H), 4.62 (s, 2H), 2.46 (m, 4H), 1.72 (m, 4H); low resolution MS (FAB)m/e 243 (MH+).

Workup

  1. temperaturethen heated to 50° C. for 1 h
  2. temperatureThe reaction mixture is cooled to 0° C.
  3. customby carefully quenching first with 0.22 mL of H2O
  4. filtrationThe resulting slurry is filtered
  5. customthe filter cake triturated with 20 mL EtOAc
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed in vacuo
  8. customPurification of the crude material
  9. distillationby Kugelrohr distillation

Sources & evidence

ORD record
ord-7c40b4cbd2594628931f3cf1b87089ba
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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