Acetyl chloride → [4-(1-Acetyl-piperidin-4-yloxy)-6-fluoro-naphthalen-2-yl]-acetic acid methyl ester

HRID 1929586Notes

Reaction equation

HRID 1929586 reaction equation
[CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[CH:14]=[C:13]([O:15][CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:22])[CH:11]=2)[CH:6]=1.[C:24](Cl)(=[O:26])[CH3:25]>O1CCCC1.CN(C)C1C=CN=CC=1>[CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[CH:14]=[C:13]([O:15][CH:16]2[CH2:17][CH2:18][N:19]([C:24](=[O:26])[CH3:25])[CH2:20][CH2:21]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:22])[CH:11]=2)[CH:6]=1

Participants

5

Reactant 2

HCID 6367Acetyl chlorideHCID 59326737[6-Fluoro-4-(piperidin-4-yloxy)-naphthalen-2-yl]-acetic acid methyl ester

Product 1

HCID 59326711[4-(1-Acetyl-piperidin-4-yloxy)-6-fluoro-naphthalen-2-yl]-acetic acid methyl esterYield 79%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of [6-fluoro-4-(piperidin-4-yloxy)-naphthalen-2-yl]-acetic acid methyl ester (the intermediate for example 4-1, 1st step, 80 mg, 0.25 mmol) and acetyl chloride (39 mg, 0.5 mmol) in tetrahydrofuran (2 mL) was added a solution of 4-dimethylaminopyridine (76 mg, 0.63 mmol) in tetrahydrofuran (1 mL) dropwise. After being stirred at room temperature overnight, the mixture was concentrated in vacuo. The residue was purified by column chromatography (gradient elution with 10-50% ethyl acetate in petroleum ether) to afford [4-(1-acetyl-piperidin-4-yloxy)-6-fluoro-naphthalen-2-yl]-acetic acid methyl ester (72 mg, 79%) as a white solid.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customThe residue was purified by column chromatography (gradient elution with 10-50% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-439472cb626f4803904ad4a078563ea0
Source dataset
uspto-grants-2012_05
Patent number
US08188090B2

Reaction notes

Loading…