Sodium hydride → tert-Butyl 4-{[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}piperidine-1-carboxylate

HRID 717870Notes

Reaction equation

HRID 717870 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[Si:17]([O:34][CH2:35][C:36]1[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[N:39]=[C:38](Cl)[CH:37]=1)([C:30]([CH3:33])([CH3:32])[CH3:31])([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O1CCCC1>[Si:17]([O:34][CH2:35][C:36]1[CH:41]=[C:40]([C:42]([F:45])([F:43])[F:44])[N:39]=[C:38]([O:3][CH:4]2[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][CH2:9]2)[CH:37]=1)([C:30]([CH3:33])([CH3:31])[CH3:32])([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 866665034-({[tert-Butyl(diphenyl)silyl]oxy}methyl)-2-chloro-6-(trifluoromethyl)pyridine

Product 1

HCID 69673501tert-Butyl 4-{[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To sodium hydride (36 mg, 0.89 mmol, 60% in mineral oil) in tetrahydrofuran (1.0 mL) was added tert-butyl 4-hydroxypiperidine-1-carboxylate (0.18 g, 0.89 mmol, Aldrich). After stirring for 45 minutes, 4-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-chloro-6-(trifluoromethyl)pyridine (0.20 g, 0.44 mmol, from Step B) in tetrahydrofuran (0.60 mL) was added and the mixture was stirred overnight. The reaction was quenched and diluted with water and extracted with ether. The extract was washed with water, brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography on silica gel, eluting with a gradient from 0-5% EtOAc in hexanes afforded product as an oil (0.19 g, 52%). LCMS (M-tBu+H)+: 559.2

Workup

  1. stirringthe mixture was stirred overnight
  2. customThe reaction was quenched
  3. additiondiluted with water
  4. extractionextracted with ether
  5. washThe extract was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washFlash chromatography on silica gel, eluting with a gradient from 0-5% EtOAc in hexanes afforded product as an oil (0.19 g, 52%)

Sources & evidence

ORD record
ord-b72b0488daa9469ca5be44d6c0620ed9
Source dataset
uspto-grants-2015_11
Patent number
US09193733B2

Reaction notes

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