Sodium Hydroxide → HCID 19787833, compound

HRID 1656316Notes

Reaction equation

HRID 1656316 reaction equation
[C:1]([O:4][C:5]1[C:10]([C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:9][C:8]([CH2:15][CH2:16][CH2:17][OH:18])=[CH:7][C:6]=1[C:19]([CH3:22])([CH3:21])[CH3:20])(=[O:3])[CH3:2].Cl.[N:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30]Cl)[CH:25]=1.[OH-].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[C:1]([O:4][C:5]1[C:6]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:7][C:8]([CH2:15][CH2:16][CH2:17][O:18][CH2:30][C:26]2[CH:25]=[N:24][CH:29]=[CH:28][CH:27]=2)=[CH:9][C:10]=1[C:11]([CH3:12])([CH3:13])[CH3:14])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 233943-(Chloromethyl)pyridine hydrochlorideHCID 19787831HCID 19787831, compound

Product 1

HCID 19787833HCID 19787833, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 1140TolueneSolvent

Procedure

A solution of 19.74 g (64.42 mmol) of 3-(4-acetoxy -3,5-di-tert-butylphenyl)propanol, 12.68 g (77.3 mmol) of 3-picolylchloride hydrochloride and 5 g of tetrabutylammonium hydrogen sulphate in 250 ml of toluene is treated with 250 ml of 50% aqueous sodium hydroxide with vigorous stirring (>400 rpm) under a nitrogen atmosphere and external cooling with a watdr-bath. Stirring of the dark reaction mixture is continued for an additional 5 hours at room temperature. After usual extractive work-up, the crude product (26.3 g) is purified by flash-chromatography over silica gel with AcOEt/H 2:1 as the eluent, yielding 16.9 g (66%) of 2,6-di-tert-butyl-4-[5-(3-pyridyl)-4-oxapentyl]phenyl acetate as a colourless oil, which is dissolved in 100 ml of dry tetrahydrofuran and added dropwise at -78° C. (acetone/dry ice) under inert conditions to a stirred suspension of 1.77 g (46.76 mmol) lithium aluminium hydride in 100 ml of anhydrous tetrahydrofuran. The reaction mixture is stirred overnight in the gradually-warming cooling bath, maintained for 2 hours at 400C, and quenched under vigorous stirring and external cooling with ice-water by sequential, careful addition of 1.77 g of water, 1.77 g of 15% aqueous sodium hydroxide and a f inal portaionn of 5.31 g of water. After 1 hour, the resulting suspension is diluted with 200 ml of THF, dried with 20 g of Na2SO4 and the aluminate precipitate is removed by filtration through a fritted glass funnel and the solvent evaporated at reduced pressure, to give 12.9 g of crude 2,6-di-tert-buty -1-4-[5-(3-pyridyl)-4-oxapentyl)phenol as a yellow solid, leaving 11.49 g (76% for the deprotection step) of pure product, m.p. 105*C, after recrystallization with n-hexane/ethyl acetate. (C23H33NO2 ; F.W. 355.5).

Workup

  1. temperatureexternal cooling with a watdr-bath
  2. stirringStirring of the dark reaction mixture
  3. customAfter usual extractive work-up, the crude product (26.3 g) is purified by flash-chromatography over silica gel with AcOEt/H 2:1 as the eluent

Sources & evidence

ORD record
ord-f439a97421c24f9ba11af560115bec4b
Source dataset
uspto-grants-1993_10
Patent number
US05254549

Reaction notes

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