Sodium borohydride → 4-tert-butyl-benzaldehyde O-[3-(4-hydroxymethyl-phenoxy)-propyl]-oxime

HRID 29657Notes

Reaction equation

HRID 29657 reaction equation
[CH:1]([C:3]1[CH:25]=[CH:24][C:6]([O:7][CH2:8][CH2:9][CH2:10][O:11][N:12]=[CH:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1)=[O:2].[BH4-].[Na+]>CO.[Cl-].[Na+].O>[OH:2][CH2:1][C:3]1[CH:4]=[CH:5][C:6]([O:7][CH2:8][CH2:9][CH2:10][O:11][N:12]=[CH:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]([CH3:21])([CH3:23])[CH3:22])=[CH:18][CH:19]=2)=[CH:24][CH:25]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 865973924-tert-butyl-benzaldehyde O-[3-(4-formyl-phenoxy)-propyl]-oxime

Product 1

HCID 865973914-tert-butyl-benzaldehyde O-[3-(4-hydroxymethyl-phenoxy)-propyl]-oxime

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 4-tert-butyl-benzaldehyde O-[3-(4-formyl-phenoxy)-propyl]-oxime (1.303 g, 3.84 mmol) in methanol (30 mL) was added sodium borohydride (0.201 g, 5.31 mmol) and the reaction was allowed to stir for 20 minutes. It was then poured slowly into brine and extracted with ethyl acetate. The combined organics were washed with brine, dried over magnesium sulfate and concentrated in vacuo to give 4-tert-butyl-benzaldehyde O-[3-(4-hydroxymethyl-phenoxy)-propyl]-oxime which was used without further purification. To a solution of 4-tert-butyl-benzaldehyde O-[3-(4-hydroxymethyl-phenoxy)-propyl]-oxime in methylene chloride (30 mL) was added phosphorus tribromide (0.400 mL, 4.25 mmol) and the reaction was stirred at room temperature for 30 minutes. It was then poured slowly over ice and extracted with ethyl acetate. The combined organics were washed with brine, dried over magnesium sulfate and concentrated in vacuo to give 4-tert-butyl-benzaldehyde O-[3-(4-bromomethyl-phenoxy)-propyl]-oxime (˜0.8 g) which was used without further purification. To a solution of 4-tert-butyl-benzaldehyde O-[3-(4-bromomethyl-phenoxy)-propyl]-oxime (−0.8 g) in tetrahydrofuran (25 mL) was added tetrabutylammonium cyanide (0.650 g, 2.42 mmol) and the reaction was allowed to stir at room temperature overnight. It was then poured into brine and extracted with ethyl acetate. The combined organics were washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography using ethyl acetate/hexanes (10/90 to 15/85) to give {4-[3-(4-tert-butyl-benzylideneaminooxy)-propoxy]-phenyl}-acetonitrile (0.607 g, 45% over 3 steps) as a colorless oil. 1H NMR (300 MHz, CDCl3); δ 8.08 (s, 1H), 7.52 (d, 2H), 7.40 (d, 2H), 7.22 (d, 2H), 6.92 (d, 2H), 4.35 (t, 2H), 4.10 (t, 2H), 3.68 (s, 2H), 2.21 (m, 2H), 1.34 (s, 9H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organics were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-170bf1e1d8f944f1b679a5cde50b80a3
Source dataset
uspto-grants-2008_09
Patent number
US07420083B2

Reaction notes

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