3-Bromopyridine → (S)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(pyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide

HRID 539070Notes

Reaction equation

HRID 539070 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1.[Si:13]([O:20][CH2:21]/[CH:22]=[N:23]/[S@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]>C1(C)C=CC=CC=1.[Cl-].[Na+].O>[Si:13]([O:20][CH2:21][C@@H:22]([NH:23][S@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]

Participants

6

Reactant 3

HCID 122863-BromopyridineHCID 16007023(NE,S)-N-[2-[tert-butyl(dimethyl)silyl]oxyethylidene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

Product 1

HCID 67033332(S)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(pyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamideYield 22.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent3×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of toluene (50 mL) cooled to −78° C. was added 2.5 M butyllithium in hexanes (6.31 mL, 15.1 mmol) and the reaction mixture was stirred until the temperature returned to −78° C. 3-Bromopyridine (1.88 g, 11.9 mmol) in toluene (5 mL) was added to the reaction mixture a rate such that the temperature never went above −65° C., and then the reaction was stirred at −78° C. for 1 hour. (S,E)-N-(2-(tert-Butyldimethylsilyloxy)ethylidene)-2-methylpropane-2-sulfinamide (3.00 g, 10.8 mmol) in toluene (1 mL) was added to the reaction mixture at a rate such that the temperature did not exceed −70° C., and then the reaction was stirred at −78° C. for 2 hours. To the −78° C. solution was added brine and the mixture partitioned between ETOAc/water. The organic layer was washed with brine, dried (phase separator silicone treated filter paper), concentrated and purified on silica gel (15-80% EtOAc in DCM) to provide (S)—N—((S)-2-(tert-butyldimethylsilyloxy)-1-(pyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide (0.862 g, 22% yield) as a yellow oil.

Workup

  1. customreturned to −78° C
  2. stirringthe reaction was stirred at −78° C. for 1 hour
  3. customdid not exceed −70° C.
  4. stirringthe reaction was stirred at −78° C. for 2 hours
  5. customthe mixture partitioned between ETOAc/water
  6. washThe organic layer was washed with brine
  7. customdried
  8. addition(phase separator silicone treated filter paper)
  9. concentrationconcentrated
  10. custompurified on silica gel (15-80% EtOAc in DCM)

Sources & evidence

ORD record
ord-4ae00342e0104c30806c00cd44c43989
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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