Water → HCID 59637583, compound

HRID 1254161Notes

Reaction equation

HRID 1254161 reaction equation
[Li]N1C(C)(C)CCC[C:3]1(C)C.[CH3:12][O:13][C:14]1[C:23]2[C:18](=[C:19]([CH3:28])[C:20]([O:26][CH3:27])=[C:21]([O:24][CH3:25])[CH:22]=2)[CH:17]=[C:16]([C:29]([OH:31])=[O:30])[CH:15]=1.CI.O>C1COCC1>[CH2:28]([C:19]1[C:20]([O:26][CH3:27])=[C:21]([O:24][CH3:25])[CH:22]=[C:23]2[C:18]=1[CH:17]=[C:16]([C:29]([OH:31])=[O:30])[CH:15]=[C:14]2[O:13][CH3:12])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 51031686HCID 51031686, compoundHCID 178418821HCID 178418821, compound

Product 1

HCID 59637583HCID 59637583, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

LTMP (7.5 mmol) is added at 0° C. to a solution of 4,6,7-trimethoxy-8-methyl-2-naphthoic acid (0.414 g, 1.5 mmol) in anhydrous THF (30 mL). The mixture is stirred for 2 h at 0° C. then trapped with MeI (0.943 mL, 15 mmol). After 2 h at 0° C., the reaction mixture is heated to ambient temperature and then hydrolysed with 30 mL of water. The aqueous phase is washed with ethyl ether (2×20 mL), acidified with 2M HCl (pH 1-2), then extracted with ethyl ether (3×30 mL). The combined organic phases are dried over MgSO4, filtered, then concentrated under reduced pressure. The residue is recrystallized (cyclohexane/ethyl acetate) to give 8-ethyl-4,6,7-trimethoxy-2-naphthoic acid (3) (0.392 g, 90%). 1H NMR (200 MHz, acetone-d6): 8.22 (s, 1H), 7.44 (s, 1H), 7.29 (s, 1H), 3.96 (s, 3H, OCH3), 3.89 (s, 3H, OCH3), 3.78 (s, 3H, OCH3), 3.02 (q, 2H, CH2), 1.16 (t, 3H, CH3). 13C NMR (100 MHz, DMSO-d6): 167.8, 154.2, 153.2, 146.9, 132.9, 127.0, 126.5, 125.0, 118.5, 102.6, 99.6, 60.6, 55.6, 55.4, 18.6, 15.4. IR (cm−1): 2940, 2826, 2637, 1682, 1464. SMHR, [M+H]+ calculated for C16H19O5: 291.1232. Found: 291.1230.

Workup

  1. waitAfter 2 h at 0° C.
  2. temperaturethe reaction mixture is heated to ambient temperature
  3. washThe aqueous phase is washed with ethyl ether (2×20 mL)
  4. extractionextracted with ethyl ether (3×30 mL)
  5. dry with materialThe combined organic phases are dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is recrystallized (cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-58e39f17229e4a93aa06cd97dd440720
Source dataset
uspto-grants-2013_06
Patent number
US08455540B2

Reaction notes

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