HCID 90460625, compound → HCID 90460827, compound

HRID 1053635Notes

Reaction equation

HRID 1053635 reaction equation
[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2[C:24](OC)=[O:25])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>C1COCC1>[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2[CH2:24][OH:25])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

3

Reactant 1

HCID 90460625HCID 90460625, compound

Product 1

HCID 90460827HCID 90460827, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

To a stirred mixture of LiAH4 (390 mg, 11.50 mmol, 1.00 equiv) in anhydrous THF (100 mL) maintained under nitrogen at −70° C. was added dropwise a solution of (R/S) methyl 5-(tert-butyldimethylsilyloxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylate (1.33 g, 3.41 mmol, 1.00 equiv) in THF. The reaction was stirred at −40° C. for 1 h and then quenched by the addition of 20 mL of saturated NH4Cl solution. The resulting mixture was concentrated under vacuum to remove the excess THF. The mixture was extracted with 3×50 mL of dichloromethane. The combined organic layers was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-20% of ethyl acetate in petroleum ether to afford 1 g (81%) of (R/S) (5-(tert-butyldimethylsilyloxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)methanol as a white solid. 1H NMR (300 MHz, CDCl3): δ 7.22 (d, J=9.0 Hz, 1H), 6.95 (d, J=2.1 Hz, 1H), 6.80 (dd, J=8.7 Hz, 2.1 Hz, 1H), 5.44-5.40 (m, 1H), 4.80 (s, 2H), 3.80-3.71 (m, 2H), 2.01-1.75 (m, 2H), 1.69-1.25 (m, 4H), 0.80 (s, 9H), 0.10 (s, 6H) ppm. LCMS (method A, ESI): RT=1.71 min, m/z=363.0 [M+H]+.

Workup

  1. customquenched by the addition of 20 mL of saturated NH4Cl solution
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customto remove the excess THF
  4. extractionThe mixture was extracted with 3×50 mL of dichloromethane
  5. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified on a silica gel column
  8. washeluted with 0-20% of ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-d144bebe830d498bb4ee0c85569cb298
Source dataset
uspto-grants-2016_07
Patent number
US09394258B2

Reaction notes

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