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 531243노트

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HRID 531243 반응식
[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

참가 물질

5

반응물 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one2회HCID 90009114(5-Bromo-2-chloropyridin-4-yl)methyl methanesulfonate2회

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
-20 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f4a537bf1d98418b8c7ae183d3e7bc25
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09353101B2

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