2,6-Lutidine → (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-chloro-6-methylpyrimidin-4-yl)oxazolidin-2-one

HRID 57354노트

반응식

HRID 57354 반응식
ClC(Cl)(O[C:5](=[O:11])[O:6][C:7](Cl)(Cl)Cl)Cl.[C:13]([O:17][C@H:18]([CH3:31])[C@H:19]([NH:22][C:23]1[CH:28]=[C:27]([CH3:29])[N:26]=[C:25]([Cl:30])[N:24]=1)CO)([CH3:16])([CH3:15])[CH3:14].N1C(C)=CC=CC=1C>C(Cl)Cl.[Cl-].[Na+]>[C:13]([O:17][C@@H:18]([C@H:19]1[CH2:7][O:6][C:5](=[O:11])[N:22]1[C:23]1[CH:28]=[C:27]([CH3:29])[N:26]=[C:25]([Cl:30])[N:24]=1)[CH3:31])([CH3:16])([CH3:14])[CH3:15]

참가 물질

6

반응물 3

HCID 79372,6-LutidineHCID 94429TriphosgeneHCID 90416038(2R,3R)-3-(tert-butoxy)-2-((2-chloro-6-methylpyrimidin-4-yl)amino)butan-1-ol

생성물 1

HCID 90414673(R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-chloro-6-methylpyrimidin-4-yl)oxazolidin-2-one수율 151.4%

시약·촉매·용매 2

HCID 5234Sodium Chloride용매HCID 6344Dichloromethane용매2회

실험 절차

Triphosgene (35 mg, 0.12 mmol, 0.4 equiv) was added to a solution of (2R,3R)-3-(tert-butoxy)-2-((2-chloro-6-methylpyrimidin-4-yl)amino)butan-1-ol (86 mg, 0.30 mmol) in DCM (3 mL) at −78° C., followed by the dropwise addition of 2,6-lutidine (0.14 mL, 1.2 mmol, 4 equiv). The solution was allowed to warm to room temperature and was then heated at 35° C. for 5 hours. The reaction was then cooled to room temperature and diluted with DCM (30 mL) and saturated aqueous sodium chloride (30 mL). The layers were separated and the organic layer was dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane) provided (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-chloro-6-methylpyrimidin-4-yl)oxazolidin-2-one (0.057 g, white solid) in 61% yield. 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 4.73 (ddd, J=8.6, 4.1, 3.0 Hz, 1H), 4.65 (dd, J=9.4, 2.9 Hz, 1H), 4.48 (m, 1H), 4.41 (m, 1H), 2.52 (s, 3H), 1.26 (s, 9H), 1.03 (d, J=6.5 Hz, 3H); MS m/z 314.1 (M+H)+; Rt-1.02 min.

후처리

  1. temperaturewas then heated at 35° C. for 5 hours
  2. temperatureThe reaction was then cooled to room temperature
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-afecba70629c4b46bd937526d5737d64
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434719B2

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