Sodium bis(2-methoxyethoxy)aluminiumhydride → [1-[1-(4-Chloro-phenyl)-cyclobutylmethyl]-azepan-3-yl]-methanol

HRID 1160344Notes

Reaction equation

HRID 1160344 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]([N:14]3[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]([CH2:21][OH:22])[CH2:15]3)=O)[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].COCCO[Al+]OCCOC.[Na+].[H-]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:12][N:14]3[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]([CH2:21][OH:22])[CH2:15]3)[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydrideHCID 21902048[1-(4-Chloro-phenyl)-cyclobutyl]-(3-hydroxymethyl-azepan-1-yl)-methanone

Product 1

HCID 58737566[1-[1-(4-Chloro-phenyl)-cyclobutylmethyl]-azepan-3-yl]-methanolYield 39%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirring 0° C. solution of [1-(4-Chloro-phenyl)-cyclobutyl]-(3-hydroxymethyl-azepan-1-yl)-methanone (0.075 g, 0.26 mmol) under N2 in toluene (2.6 mL, 0.1M) was added sodium bis(2-methoxyethoxy)aluminum hydride (65+weight % in toluene) (0.28 mL, 0.91 mmol) dropwise with stirring. When the reaction was complete by HPLC, the reaction was quenched with H2O. 10% NaOH and ethyl acetate were added, and the organic was removed, dried with Na2SO4, and concentrated. The crude reaction mixture was purified by silica gel:chromatography (90:8:2 Hexanes:methylene chloride: 2N NH3 in ethyl alcohol). A 39% yield (0.0290 g) of pure material was obtained as well as other impure fractions. 1H NMR (CDCl3, 300 MHz) 7.28-7.25 (2H, m), 7.15-7.09 (2H, m), 3.44 (1H, dd, J=10.5, 4.5 Hz), 3.27 (1H, dd, J=10.3, 5.5 Hz), 2.89 (1H, d, J=13.9 Hz), 2.83 (1H, d, J=13.9 Hz), 2.72-2.60 (1H, m), 2.50-1.10 (16H, m) ppm. 13C NMR (CDCl3, 75 MHz) 146.5, 131.22, 128.10, 127.93, 70.95, 67.49, 61.85, 59.10, 47.62, 40.59, 32.12, 31.90, 29.92, 25.41, 16.20 ppm. LRMS: 308.24.

Workup

  1. customthe reaction was quenched with H2O
  2. addition10% NaOH and ethyl acetate were added
  3. customthe organic was removed
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated
  6. customThe crude reaction mixture
  7. customwas purified by silica gel

Sources & evidence

ORD record
ord-4030b5bdb5024f2f9b88068ee4df8f90
Source dataset
uspto-grants-2010_10
Patent number
US07816375B2

Reaction notes

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