1,2-Dimethoxyethane → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(6-isopropenylpyridin-2-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1028583

반응식

HRID 1028583 반응식
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([CH3:10])=[CH2:9])[N:3]=1.[F:11][C:12]([F:51])([F:50])[C:13]1[CH:14]=[C:15]([C@H:23]2[O:27][C:26](=[O:28])[N:25]([CH2:29][C:30]3[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=3B3OC(C)(C)C(C)(C)O3)[C@H:24]2[CH3:49])[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1.COCCOC.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO>[F:51][C:12]([F:11])([F:50])[C:13]1[CH:14]=[C:15]([C@H:23]2[O:27][C:26](=[O:28])[N:25]([CH2:29][C:30]3[CH:35]=[C:34]([C:36]([F:37])([F:38])[F:39])[CH:33]=[CH:32][C:31]=3[C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([CH3:10])=[CH2:9])[N:3]=3)[C@H:24]2[CH3:49])[CH:16]=[C:17]([C:19]([F:20])([F:22])[F:21])[CH:18]=1

참가 물질

7

반응물 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 221642832-Bromo-6-(prop-1-en-2-yl)pyridineHCID 57704783(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one

생성물 1

HCID 11721263(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(6-isopropenylpyridin-2-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매

반응 조건

온도
100 °C

실험 절차

In a tube were placed 2-bromo-6-isopropenylpyridine (17.5 mg, 0.0878 mmol), (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one (26.2 mg, 0.0439 mmol), DME (190 μL), EtOH (62 μL), and 1M aqueous Na2CO3 (100 μL, 0.1 mmol). The mixture was degassed with N2. Next, Pd(PPh3)4 (9 mg, 7.8×10−3 mmol) was added and the mixture was degassed again with N2. The tube was sealed and heated at 100° C. for 2 hours. The reaction was then cooled to room temperature, diluted with EtOAc (50 mL), and washed with water and brine (15 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (5 to 25% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(6-isopropenylpyridine-2-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.15 (15% EtOAc/hexanes). LCMS=589.1 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.81-7.85 (m, 2H), 7.74 (s, 1H), 7.69-7.69 (m, 3H), 7.58 (d, J=8.0 Hz, 1H), 7.53 (d, J=7.7 Hz, 1H), 7.34 (d, J=7.6 Hz, 1H), 5.94 (s, 1H), 5.48 (d, J=7.7 Hz, 1H), 5.36 (s, 1H), 5.06 (d, J=16.0 Hz, 1H), 4.47 (d, J=16.1 Hz, 1H), 3.91 (m, 1H), 2.23 (s, 3H), 0.50 (d, J=6.6 Hz, 3H).

후처리

  1. customIn a tube were placed
  2. customThe mixture was degassed with N2
  3. customthe mixture was degassed again with N2
  4. customThe tube was sealed
  5. temperatureThe reaction was then cooled to room temperature
  6. additiondiluted with EtOAc (50 mL)
  7. washwashed with water and brine (15 mL each)
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification of the residue by flash chromatography on silica gel (5 to 25% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-7e253171e74c433c83d78bb0f2e84d60
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735435B2

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