Carbon Dioxide → 4-(2-Ethylpiperidin-1-yl)-3-(methoxymethyl)benzoic acid hydrochloride

HRID 1630982Notes

Reaction equation

HRID 1630982 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]2[CH2:14][CH3:15])=[C:4]([CH2:16][O:17][CH3:18])[CH:3]=1.C([Li])CCC.[C:24](=[O:26])=[O:25].[ClH:27]>C1COCC1>[ClH:27].[CH2:14]([CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][N:8]1[C:5]1[CH:6]=[CH:7][C:2]([C:24]([OH:26])=[O:25])=[CH:3][C:4]=1[CH2:16][O:17][CH3:18])[CH3:15]

Participants

6

Reactant 4

HCID 280Carbon Dioxide2×HCID 313Hydrochloric AcidHCID 585541651-(4-Bromo-2-(methoxymethyl)phenyl)-2-ethylpiperidineHCID 178418339Butyllithium

Product 1

HCID 1317314304-(2-Ethylpiperidin-1-yl)-3-(methoxymethyl)benzoic acid hydrochlorideYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[4-bromo-2-(methoxymethyl)phenyl]-2-ethylpiperidine (1.42 g, 4.55 mmol) in anhydrous THF was added n-butyl lithium (2.4 mL, 6.82 mmol) in drops at −78° C. After 1 hour at −78° C., the reaction mixture was poured onto crushed dry-ice (100 g). Once the excess carbon dioxide was escaped, the reaction mixture was acidified with 2N HCl. The precipitate was filtered off and dried to afford the title compound as a solid (1.0 g, 70%). HPLC (Method A), Rt: 2.5 min (purity: 97.7%). LC/MS, M+(ESI): 278.0. 1H NMR (CD3OD, 400 MHz) δ 8.20 (1H, d), 8.07 (1H, s), 7.92 (1H, d), 5.05 (2H, m), 3.89 (1H, bs), 3.69 (4H, m), 2.39 (1H, d), 2.02-2.14 (2H, m), 1.72-1.95 (3H, m), 1.46 (2H, m), 0.88 (3H, t).

Workup

  1. additionthe reaction mixture was poured
  2. filtrationThe precipitate was filtered off
  3. customdried

Sources & evidence

ORD record
ord-feb9e44d612945ee968f85207e3404f4
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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