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

HRID 2410491Notes

Reaction equation

HRID 2410491 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 a 2N aqueous solution of 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 (Method A): 278.0 (M+H)+. 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-a1cbbb2dc730482babb5193667e01d2d
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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