Sodium hydride → (2R)-4-(3-Pyridyl)-1-(6-(3,3,3-trifluoropropoxy)naphthalen-2-yloxy)-2-butanol

HRID 1600968Notes

Reaction equation

HRID 1600968 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH2:13][CH2:14][C:15]([F:18])([F:17])[F:16])[CH:8]=2)[CH:3]=1.C1(C)C=CC(S(O[CH2:29][C@H:30]([O:39][Si](C(C)(C)C)(C)C)[CH2:31][CH2:32][C:33]2[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=2)(=O)=O)=CC=1.[H-].[Na+].O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C)C=O.O1CCCC1.O>[N:35]1[CH:36]=[CH:37][CH:38]=[C:33]([CH2:32][CH2:31][C@@H:30]([OH:39])[CH2:29][O:1][C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH2:13][CH2:14][C:15]([F:16])([F:17])[F:18])[CH:8]=3)[CH:3]=2)[CH:34]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 162116731-Butanaminium, N,N,N-tributyl-, fluoride, hydrateHCID 218307112-Hydroxy-6-(3,3,3-trifluoropropoxy)naphthaleneHCID 54162583(2R)-2-(tert-butyldimethylsilyloxy)-4-(3-pyridyl)-1-butyl para-toluenesulfonate

Product 1

HCID 54174222(2R)-4-(3-Pyridyl)-1-(6-(3,3,3-trifluoropropoxy)naphthalen-2-yloxy)-2-butanolYield 64.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Prepared according to the method described in example 26e) from 2-hydroxy-6-(3,3,3-trifluoropropoxy)naphthalene (0.212 g), (2R)-2-(tert-butyldimethylsilyloxy)-4-(3-pyridyl)-1-butyl para-toluenesulfonate (0.30 g) and sodium hydride (60%, 33 mg) in dimethylformamide (3 ml) with heating at 60° C. for 2 hours. The adduct was dissolved in tetrahydrofuran (10 ml) and tetrabutylammonium fluoride hydrate (0.30 g) was added. After 2 hours, the mixture was diluted with water and extracted with ether. The organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica eluting with hexane:acetone (3:2) to give the title compound (0.18 g) which was recrystallised from ethyl acetate:hexane.

Workup

  1. customPrepared
  2. extractionextracted with ether
  3. dry with materialThe organic extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography over silica eluting with hexane:acetone (3:2)

Sources & evidence

ORD record
ord-afdf9e1b86284e5984ea0d14d1cb1624
Source dataset
uspto-grants-1999_11
Patent number
US05977105

Reaction notes

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