Water → (S)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(5-fluoropyridin-2-yl)ethyl)-2-methylpropane-2-sulfinamide

HRID 539096Notes

Reaction equation

HRID 539096 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][N:8]=1.[Si:14]([O:21][CH2:22]/[CH:23]=[N:24]/[S@:25]([C:27]([CH3:30])([CH3:29])[CH3:28])=[O:26])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].O>C1(C)C=CC=CC=1>[Si:14]([O:21][CH2:22][C@@H:23]([NH:24][S@:25]([C:27]([CH3:30])([CH3:29])[CH3:28])=[O:26])[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][N:8]=1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 962WaterHCID 27831712-Bromo-5-fluoropyridineHCID 16007023(NE,S)-N-[2-[tert-butyl(dimethyl)silyl]oxyethylidene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

Product 1

HCID 67033342(S)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(5-fluoropyridin-2-yl)ethyl)-2-methylpropane-2-sulfinamideYield 48.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of toluene (500 mL) at −78° C. was added butyl lithium (1.6 M in hexanes, 75.6 ml, 121 mmol) at a rate such that the internal temperature did not exceed −50° C. To this solution was added 2-bromo-5-fluoropyridine (23.2 g, 132 mmol) in toluene (200 mL) at a rate such that the internal temperature did not exceed −68° C. The reaction was stirred at −78° C. for 1 hour. To the reaction was added (S,E)-N-(2-(tert-butyldimethylsilyloxy)ethylidene)-2-methylpropane-2-sulfinamide (30.5 g, 110 mmol) in toluene (200 mL) at a rate such that the internal temperature did exceed −68° C. The reaction was again stirred at −78° C. for 1 hour. To the reaction was added 200 mL of water and the layers separated. The toluene solution was washed with water (200 mL), brine (200 mL), dried over MgSO4 and concentrated in vacuo. The crude material was chromatographed using 4:1 hexanes/ethyl acetate as eluent to yield (S)—N—((S)-2-(tert-butyldimethylsilyloxy)-1-(5-fluoropyridin-2-yl)ethyl)-2-methylpropane-2-sulfinamide (20 g, 48%).

Workup

  1. customdid not exceed −50° C
  2. customdid not exceed −68° C
  3. customdid exceed −68° C
  4. stirringThe reaction was again stirred at −78° C. for 1 hour
  5. customthe layers separated
  6. washThe toluene solution was washed with water (200 mL), brine (200 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe crude material was chromatographed

Sources & evidence

ORD record
ord-c5c7ecdef783459a8bad138ffcba0c8b
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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