Sodium hydride → tert-Butyl 4-(2-methyl-2-(4-nitronaphthalen-1-yloxy)propyl)pyridin-2-ylcarbamate

HRID 1916812노트

반응식

HRID 1916812 반응식
[OH:1][C:2]([CH3:19])([CH3:18])[CH2:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=1.[H-].[Na+].F[C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([N+:33]([O-:35])=[O:34])=[CH:25][CH:24]=1>CN(C=O)C>[CH3:18][C:2]([O:1][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([N+:33]([O-:35])=[O:34])=[CH:25][CH:24]=1)([CH3:19])[CH2:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:16])[CH3:15])[CH:5]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 2617641-Fluoro-4-nitronaphthaleneHCID 58416752tert-Butyl 4-(2-hydroxy-2-methylpropyl)pyridin-2-ylcarbamate

생성물 1

HCID 67395048tert-Butyl 4-(2-methyl-2-(4-nitronaphthalen-1-yloxy)propyl)pyridin-2-ylcarbamate수율 16.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
0 °C

실험 절차

To a stirred solution of tert-butyl 4-(2-hydroxy-2-methylpropyl)pyridin-2-ylcarbamate (26) (292 mg, 1.10 mmol) in DMF (5.0 mL), at 0° C. under nitrogen, was added sodium hydride (132 mg, 3.29 mmol, 60 wt %). The resulting orange mixture was stirred at 0° C. for 45 min, and then a solution of 1-fluoro-4-nitronaphthalene (210 mg, 1.10 mmol) in DMF (5.0 mL) was added dropwise, over 2 min. The dark-brown mixture was stirred at 0° C. for 5 min, and then at RT. After 90 min, the reaction was quenched by addition of 4.0 mL aqueous NH4Cl solution. Diethyl ether (40 mL), EtOAc (40 mL) and water (40 mL) were added, and the layers separated. The aqueous layer was extracted with a mixture of diethyl ether and EtOAc (1:1, 30 mL×2). The combined organic extracts were washed with brine (50 mL), dried and the solvents removed under reduced pressure. The crude mixture was purified by column chromatography (40 g) eluting with 0 to 70% EtOAc in iso-hexane, to give tert-butyl 4-(2-methyl-2-(4-nitronaphthalen-1-yloxy)propyl)pyridin-2-ylcarbamate (27) (79 mg, 15%) as an orange foam: m/z 438 (M+H)+ (ES+).

후처리

  1. stirringThe dark-brown mixture was stirred at 0° C. for 5 min
  2. customat RT
  3. waitAfter 90 min
  4. customthe reaction was quenched by addition of 4.0 mL aqueous NH4Cl solution
  5. additionDiethyl ether (40 mL), EtOAc (40 mL) and water (40 mL) were added
  6. customthe layers separated
  7. extractionThe aqueous layer was extracted with a mixture of diethyl ether and EtOAc (1:1, 30 mL×2)
  8. washThe combined organic extracts were washed with brine (50 mL)
  9. customdried
  10. customthe solvents removed under reduced pressure
  11. customThe crude mixture was purified by column chromatography (40 g)
  12. washeluting with 0 to 70% EtOAc in iso-hexane

출처 및 근거

ORD 기록
ord-1933cf53f8264b13ada78c07986523be
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618140B2

반응 노트

불러오는 중…