Hydrochloric Acid → [6-Fluoro-4-(piperidin-4-yloxy)-naphthalen-2-yl]-acetic acid methyl ester

HRID 1929584Notes

Reaction equation

HRID 1929584 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=3)[CH:18]=[C:17]([CH2:26][C:27]([O:29][CH3:30])=[O:28])[CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>CO>[CH3:30][O:29][C:27](=[O:28])[CH2:26][C:17]1[CH:16]=[C:15]([O:14][CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=2)[CH:18]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 593267504-(7-Fluoro-3-methoxycarbonylmethyl-naphthalen-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 59326737[6-Fluoro-4-(piperidin-4-yloxy)-naphthalen-2-yl]-acetic acid methyl esterYield 85%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of 4-(7-fluoro-3-methoxycarbonylmethyl-naphthalen-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (prepared as described above, 400 mg, 0.99 mmol) in methanol (4 mL) was added a 5N solution of hydrogen chloride in methanol (4 mL). After being stirred at room temperature for 3 hours, the mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (10 mL), and treated with a saturated aqueous sodium bicarbonate solution (10 mL). The aqueous layer was separated and extracted with dichloromethane (10 mL×2). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (elution with 10% methanol in dichloromethane) to afford [6-fluoro-4-(piperidin-4-yloxy)-naphthalen-2-yl]-acetic acid methyl ester (260 mg, 85%) as a pale yellow solid.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  3. additiontreated with a saturated aqueous sodium bicarbonate solution (10 mL)
  4. customThe aqueous layer was separated
  5. extractionextracted with dichloromethane (10 mL×2)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (elution with 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-fef8e4deb471459c9202c55b8b3fea7e
Source dataset
uspto-grants-2012_05
Patent number
US08188090B2

Reaction notes

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