Sodium bis(trimethylsilyl)amide → (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-[(5-bromo-2-chloropyridin-4-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

HRID 531243Notes

Reaction equation

HRID 531243 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[NH:15][C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].CS(O[CH2:37][C:38]1[C:43]([Br:44])=[CH:42][N:41]=[C:40]([Cl:45])[CH:39]=1)(=O)=O>CN(C=O)C>[F:21][C:2]([F:1])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:37][C:38]3[C:43]([Br:44])=[CH:42][N:41]=[C:40]([Cl:45])[CH:39]=3)[C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one2×HCID 90009114(5-Bromo-2-chloropyridin-4-yl)methyl methanesulfonate2×

Product 1

HCID 118021439(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-[(5-bromo-2-chloropyridin-4-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-20 °C

Procedure

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 4, 1.305 g, 4.17 mmol) in 30 mL of DMF was cooled to −20° C. NaHMDS (1.0 M, 4.17 ml, 4.17 mmol) was added and the reaction was stirred at −20° C. for 20 minutes. Next, a solution of (5-bromo-2-chloropyridin-4-yl)methyl methanesulfonate (INTERMEDIATE 28, 1.2522 g, 4.17 mmol) in 5 mL of DMF was added and the solution turned brown. The reaction was warmed to 0° C. by switching to an ice/water bath and the reaction stirred for an additional 30 minutes, at which time an LCMS aliquot confirmed the reaction was complete. It was quenched with aqueous NaHCO3. The reaction was extracted with ethyl acetate, then washed with aqueous NaHCO3 and brine, dried with Na2SO4, filtered and the filtrate was concentrated. The crude oil was purified by silica gel chromatography to give the titled compound as an off-white solid. 1H NMR (CDCl3, 500 MHz): δ 8.52 (s, 1H), 7.92 (s, 1H), 7.80 (s, 2H), 7.36 (s, 1H), 5.81 (d, 1H), 4.78 (d, 1H), 4.34 (d, 1H), 4.17 (m, 1H), 0.82 (d, 3H).

Workup

  1. temperatureThe reaction was warmed to 0° C.
  2. customby switching to an ice/water bath
  3. stirringthe reaction stirred for an additional 30 minutes, at which time an LCMS aliquot
  4. customIt was quenched with aqueous NaHCO3
  5. extractionThe reaction was extracted with ethyl acetate
  6. washwashed with aqueous NaHCO3 and brine
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated
  10. customThe crude oil was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f4a537bf1d98418b8c7ae183d3e7bc25
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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