Ethanol, 2-chloro-, 1-(4-methylbenzenesulfonate) → 4-[2-(2-Chloro-ethoxy)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2377799Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[OH:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:21][CH2:22][CH2:23]OS(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH2:23][CH2:22][Cl:21])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 4-(2-hydroxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester Compound 2a (0.67 g, 2.42 mmol), toluene-4-sulfonic acid 2-chloro-ethyl ester Compound 2b (1.13 g, 4.84 mmol), Cs2CO3 (1.60 g, 4.84 mmol) and DMF (20 mL) were heated and stirred at 50° C. overnight (18 hrs). The excess DMF was removed under reduced pressure and the white residue was mixed with AcOEt (100 mL), washed with water and dried over Na2SO4. The filtered dry solution was evaporated and the product was purified via flash chromatography (silica gel, 25% AcOEt/hexane) to provide 4-[2-(2-chloro-ethoxy)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester Compound 2c (0.78 g, 95%) as a colorless sticky oil. LC-MS (3.943 min.) m/z 362.1 (M+Na+).

Workup

customThe excess DMF was removed under reduced pressure
additionthe white residue was mixed with AcOEt (100 mL)
washwashed with water
dry with materialdried over Na2SO4
customThe filtered dry solution was evaporated
customthe product was purified via flash chromatography (silica gel, 25% AcOEt/hexane)

Sources & evidence

ORD record: ord-31d1abad51e2454aa1c42e801d0c993c
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07470711B2

Reaction notes

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