Aluminium lithium hydride → (R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutan-1-ol

HRID 660370Notes

Reaction equation

HRID 660370 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH3:7][O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH2:21][C@H:22]([CH:26]([CH3:28])[CH3:27])[C:23](O)=[O:24])[CH:19]=2)[CH:14]=[N:13]1>C1COCC1>[CH3:7][O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH2:21][C@H:22]([CH:26]([CH3:28])[CH3:27])[CH2:23][OH:24])[CH:19]=2)[CH:14]=[N:13]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 68783318(R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutanoic acid

Product 1

HCID 68781374(R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutan-1-olYield 79.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of LiAlH4 (40 mg, 1 mmol) in anhydrous THF (2 mL) under N2 at −78° C. was added dropwise a solution of (R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutanoic acid (150 mg, 0.5 mmol) in anhydrous THF (1 mL). The mixture was allowed to warm to rt and stirred for 24 h. TLC showed the starting material had been consumed. The mixture was cooled to 0° C., H2O (40 uL) was added dropwise, followed by 10% aq NaOH (40 uL). The mixture was filtered and the filtrate was evaporated. The residue was partitioned between EtOAc and water, and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated to give (R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutan-1-ol (115 mg, 79%). 1H NMR (400 MHz, CDCl3): 1.00 (m, 6H), 1.72 (m, 3H), 2.16 (m, 2H), 2.68 (m, 1H), 2.88 (m, 1H), 3.27 (m, 2H), 3.29 (s, 3H), 3.58 (m, 2H), 4.48 (m, 2H), 7.00 (m, 1H), 7.23 (m, 1H), 7.62 (m, 1H), 7.96 (m, 1H); MS: 291 (M++1)

Workup

  1. customhad been consumed
  2. temperatureThe mixture was cooled to 0° C.
  3. additionH2O (40 uL) was added dropwise
  4. filtrationThe mixture was filtered
  5. customthe filtrate was evaporated
  6. customThe residue was partitioned between EtOAc and water
  7. extractionextracted with EtOAc (3×10 mL)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-c4b61c1610aa490380cca1035724dc05
Source dataset
uspto-grants-2011_12
Patent number
US08084485B2

Reaction notes

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