2-Bromo-5-fluoropyridine → (RS)-N-[(1R)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-(5-fluoropyridin-2-yl)ethyl]-2-methylpropane-2-sulfinamide

HRID 450371Notes

Reaction equation

HRID 450371 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[Li]C(C)(C)C.[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].[Li]>CCOCC>[Si:14]([O:21][CH2:22][C@H:23]([NH:24][S:25]([C:27]([CH3:30])([CH3:29])[CH3:28])=[O:26])[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 27831712-Bromo-5-fluoropyridineHCID 3028194LithiumHCID 86644143(R,E)-N-(2-((tert-butyldimethylsilyl)oxy)ethylidene)-2-methylpropane-2-sulfinamide2×HCID 178418306HCID 178418306, compound

Product 1

HCID 68479628(RS)-N-[(1R)-2-{[tert-Butyl(dimethyl)silyl]oxy}-1-(5-fluoropyridin-2-yl)ethyl]-2-methylpropane-2-sulfinamide

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
-70 °C

Procedure

To a cold solution of 2-bromo-5-fluoropyridine (1.3 g, 7.2 mmol) in Et2O (8 ml) at −68° C. was added a solution of t-BuLi (1.7 M in pentane, 8.5 ml, 14.4 mmol) carefully. The temperature of the mixture was kept below −65° C. and the mixture was allowed to stir for 15 minutes at −70° C. A solution of (R)—N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethylidene)-2-methylpropane-2-sulfinamide (Intermediate 21, 1.0 g, 3.6 mmol) in Et2O (24 ml) was cooled to −75° C. To it was cannulated a solution of the above lithium compound for a duration of 15 minutes. More Et2O (2 ml) was used to rinse the lithium compound solution. The mixture was allowed to stir at −78° C. for 3 hours. To it was added saturated NH4Cl solution. EtOAc was added and the organic layer was washed with brine and concentrated. Column chromatography (20-40% EtOAc in hexanes) gave the desired product (RS)—N-[(1R)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-(5-fluoropyridin-2-yl)ethyl]-2-methylpropane-2-sulfinamide* as a solid (higher Rf on TLC, 1.19 g) together with diastereoisomer (lower Rf on TLC, 166 mg). 1H NMR (300 MHz, CDCl3) □ ppm 8.41 (s, 1H) 7.35 (d, J=6.78 Hz, 2H) 4.59 (t, J=5.65 Hz, 1H) 4.43 (d, J=5.28 Hz, 1H) 3.82-4.02 (m, 2H) 1.23 (s, 9H) 0.81 (s, 9H)-0.06 (d, J=12.06 Hz, 6H).

Workup

  1. customwas kept below −65° C.
  2. washto rinse the lithium compound solution
  3. stirringto stir at −78° C. for 3 hours
  4. additionTo it was added saturated NH4Cl solution
  5. additionEtOAc was added
  6. washthe organic layer was washed with brine
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c09047f82db244468db60d35fb2309d4
Source dataset
uspto-grants-2013_07
Patent number
US08486966B2

Reaction notes

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