Carbon Dioxide → 3-(Methoxymethyl)-4-(2-methylpiperidin-1-yl)benzoic acid

HRID 1630970

반응식

HRID 1630970 반응식
C([Li])(C)(C)C.CCCCC.Br[C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]2[CH3:24])=[C:14]([CH2:25][O:26][CH3:27])[CH:13]=1.[C:28](=[O:30])=[O:29]>CCOCC.CCOCC.CCOC(C)=O>[CH3:27][O:26][CH2:25][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[N:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]1[CH3:24])[C:28]([OH:30])=[O:29]

참가 물질

7

반응물 4

HCID 280Carbon DioxideHCID 8003PentaneHCID 585541231-(4-Bromo-2-(methoxymethyl)phenyl)-2-methylpiperidineHCID 178418306HCID 178418306, 화합물

생성물 1

HCID 594958043-(Methoxymethyl)-4-(2-methylpiperidin-1-yl)benzoic acid

시약·촉매·용매 2

HCID 3283Diethyl Ether용매2회HCID 21584169Diethylether ethylacetate용매

반응 조건

온도
-78 °C

실험 절차

A 1.5M solution of tert-butyllithium in pentane (64 mL, 95 mmol) was added into anhydrous Et2O (130 mL) cooled at −78° C. A solution of 1-[4-bromo-2-(methoxymethyl)phenyl]-2-methylpiperidine (13.0 g, 43.5 mmol) in anhydrous Et2O (20 mL) was added slowly. After 40 minutes, the reaction mixture was poured on an excess of freshly crushed dry ice and stirred for 30 min. The mixture was diluted with Et2O/EtOAc (1:1, 800 mL) and washed with water (200 mL, pH=4-5 adjusted with a 5N aqueous solution of HCl). The aqueous layer was extracted with EtOAc (400 mL). The organic layers were combined, dried (MgSO4) and the solvents were removed under reduced pressure to give a yellow oil, which was triturated in iPr2O (˜20 mL) and pentane (˜20 mL). The precipitate was filtered off, washed with pentane and dried under reduced pressure to give the title compound as a beige powder. HPLC (Method A), Rt: 1.6 min (purity: 93.5%). UPLC/MS, M+(ESI): 264.2, M−(ESI): 262.2. 1H NMR (CDCl3, 300 MHz) δ 8.22 (d, J=2.1 Hz, 1H), 8.00 (dd, J=8.3, 2.1 Hz, 1H), 7.17 (d, J=8.3 Hz, 1H), 4.60 (d, J=12.3 Hz, 1H), 4.55 (d, J=12.3 Hz, 1H), 3.46 (s, 3H), 3.17 (m, 1H), 3.02 (m, 1H), 2.63 (m, 1H), 1.88-1.65 (m, 4H), 1.55-1.40 (m, 2H), 0.88 (d, J=6.2 Hz, 3H).

후처리

  1. washwashed with water (200 mL, pH=4-5
  2. extractionThe aqueous layer was extracted with EtOAc (400 mL)
  3. dry with materialdried (MgSO4)
  4. customthe solvents were removed under reduced pressure
  5. customto give a yellow oil, which
  6. customwas triturated in iPr2O (˜20 mL)
  7. filtrationThe precipitate was filtered off
  8. washwashed with pentane
  9. customdried under reduced pressure

출처 및 근거

ORD 기록
ord-6240eaa076604fc698913272cbcc3ae9
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791142B2

연결된 노트

불러오는 중…