Hydrogen Bromide → 5-Fluoro-3H-spiro[benzofuran-2,4'-piperidine]

HRID 2112733

반응식

HRID 2112733 반응식
Br.[F:2][C:3]1[CH:4]=[CH:5][C:6]([O:24]C)=[C:7]([CH:23]=1)[CH2:8][C:9]1(O)[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]1.O>C(O)(=O)C>[F:2][C:3]1[CH:4]=[CH:5][C:6]2[O:24][C:9]3([CH2:10][CH2:11][NH:12][CH2:13][CH2:14]3)[CH2:8][C:7]=2[CH:23]=1

참가 물질

5

반응물 3

HCID 260Hydrogen Bromide2회HCID 962WaterHCID 59833653Tert-butyl 4-(5-fluoro-2-methoxybenzyl)-4-hydroxypiperidine-1-carboxylate

생성물 1

HCID 574943045-Fluoro-3H-spiro[benzofuran-2,4'-piperidine]수율 38.1%

시약·촉매·용매 1

HCID 176Acetic Acid용매

실험 절차

Hydrobromic acid (48%, 60 mL) was added to a solution of the crude tert-butyl 4-(5-fluoro-2-methoxybenzyl)-4-hydroxypiperidine-l-carboxylate (86 g) in acetic acid (300 mL). The mixture was heated at reflux for 5 hours. Further hydrobromic acid (48%, 60 mL) was added and reflux continued for 24 hours. The mixture was cooled to room temperature, added to water (2 L) and extracted with tert.-butyl methyl ether (2×500 mL). The aqueous phase was adjusted to pH>10 by addition of 50 wt. % sodium hydroxide solution and extracted with tert.-butyl methyl ether (2L+1L). Organic extracts were dried over anhydrous magnesium sulphate, filtered and evaporated under reduced pressure. The residual solid was crystallised from tetrahydrofuran/tert.-butyl methyl ether (4:1, 500 mL) to give the title compound (20 g). 1H-NMR (CD3OD, 400 MHz): δ 6.92-6.87 (m, 1H); 6.81-6.75 (m, 1H); 6.64 (dd, J=4.2, 8.7 Hz, 1H); 3.08-2.98 (m, 4H); 2.89-2.81 (m, 2H); 1.91-1.83 (m, 2H); 1.78-1.69 (m, 2H).

후처리

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 5 hours
  3. temperaturereflux
  4. extractionextracted with tert.-butyl methyl ether (2×500 mL)
  5. additionThe aqueous phase was adjusted to pH>10 by addition of 50 wt. % sodium hydroxide solution
  6. extractionextracted with tert.-butyl methyl ether (2L+1L)
  7. dry with materialOrganic extracts were dried over anhydrous magnesium sulphate
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customThe residual solid was crystallised from tetrahydrofuran/tert.-butyl methyl ether (4:1, 500 mL)

출처 및 근거

ORD 기록
ord-b136b9a7e601414e927540b5ee85242b
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07524856B2

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