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

HRID 2410477

Reaction equation

HRID 2410477 reaction equation
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]

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 21584169Diethylether ethylacetateSolvent

Conditions

Temperature
-78 °C

Procedure

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%). HPLC/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).

Workup

  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

Sources & evidence

ORD record
ord-28e16b203b4d41e895c700bb74d67b6b
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Linked notes

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