Lithium tri-tert-butoxyaluminohydride → (1S,2R,4S,7S)-7-{[9-(tert-butyldimethylsilanyloxy)nonyl]methylamino}-bicyclo[2.2.1]heptan-2-ol

HRID 1670896Notes

Reaction equation

HRID 1670896 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][N:18]([CH3:27])[C@H:19]1[C@H:23]2[CH2:24][CH2:25][C@@H:20]1[C:21](=[O:26])[CH2:22]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].C(O[Al](OC(C)(C)C)OC(C)(C)C)(C)(C)C.[Li+]>C1COCC1>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][N:18]([CH3:27])[C@H:19]1[C@H:23]2[CH2:24][CH2:25][C@@H:20]1[C@H:21]([OH:26])[CH2:22]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 16710494Lithium tri-tert-butoxyaluminohydride2×HCID 67348380(1S,4S,7S)-7-{[9-(tert-butyldimethylsilanyloxy)nonyl]methylamino}-bicyclo[2.2.1]heptan-2-one

Product 1

HCID 67348477(1S,2R,4S,7S)-7-{[9-(tert-butyldimethylsilanyloxy)nonyl]methylamino}-bicyclo[2.2.1]heptan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1S,4S,7S)-7-{[9-(tert-butyldimethylsilanyloxy)nonyl]methylamino}-bicyclo[2.2.1]heptan-2-one (4.11 g, 10.4 mmol max) in dry THF (41 mL) at −5° C. under a nitrogen atmosphere was added lithium tri-tert-butoxyaluminum hydride (3.44 g, 13.5 mmol). After 1.5 h at −5° C. more lithium tri-tert-butoxyaluminum hydride (2.64 g, 10.4 mmol) was added. After 1 h at −5° C. the reaction was quenched with satd ammonium chloride solution (aq) and partitioned between ethyl acetate and water. The solids were removed by filtration and washed with ethyl acetate. The phases were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with satd NaHCO3 (aq), brine, dried (Na2SO4), filtered, and concentrated to dryness to afford a turbid yellow oil. The crude product was purified by column chromatography over silica gel using a gradient of 7.5-10% MeOH/DCM as eluent. After evaporation of the volatiles a light yellow/brown viscous oil was obtained.

Workup

  1. customAfter 1 h at −5° C. the reaction was quenched with satd ammonium chloride solution (aq)
  2. custompartitioned between ethyl acetate and water
  3. customThe solids were removed by filtration
  4. washwashed with ethyl acetate
  5. customThe phases were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined organic layers were washed with satd NaHCO3 (aq), brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customto afford a turbid yellow oil
  12. customThe crude product was purified by column chromatography over silica gel using a gradient of 7.5-10% MeOH/DCM as eluent
  13. customAfter evaporation of the volatiles a light yellow/brown viscous oil
  14. customwas obtained

Sources & evidence

ORD record
ord-76defe19c8874ca0b1a82bc492e2bd36
Source dataset
uspto-grants-2011_08
Patent number
US07994211B2

Reaction notes

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