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

HRID 720028Notes

Reaction equation

HRID 720028 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 chromatography (90:8:2 Hexanes:methylene chloride:2N NH3 in ethyl alcohol)

Sources & evidence

ORD record
ord-d077744cf65e42da97259e3887381449
Source dataset
uspto-grants-2006_11
Patent number
US07132551B2

Reaction notes

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