Bis(2-bromoethyl) ether → 4-(4-TRIFLUOROMETHYLPHENYL)TETRAHYDRO-2H-PYRAN-4-CARBOXYLIC ACID

HRID 1868633Notes

Reaction equation

[H-].[Na+].[F:3][C:4]([F:18])([F:17])[C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([O:14]CC)=[O:13])=[CH:7][CH:6]=1.Br[CH2:20][CH2:21][O:22][CH2:23][CH2:24]Br>CN1C(=O)CCC1.Cl>[F:18][C:4]([F:3])([F:17])[C:5]1[CH:6]=[CH:7][C:8]([C:11]2([C:12]([OH:14])=[O:13])[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A suspension of NaH (60% dispersion in mineral oil (2.3 g, 60 mmol)) in NMP (80 mL) was cooled to 0° C. under nitrogen. The reaction mixture was treated with a solution of ethyl 2-(4-(trifluoromethyl)phenyl)acetate (4.672 g, 20 mmol) in NMP (20 mL) in a dropwise fashion over 10 minutes (effervescence occurred), followed by bis(2-bromoethyl)ether (2.8 mL, 22 mmol). After 15 minutes, the reaction was warmed to 23° C. After 20 hours, the reaction was diluted with a 10% HCl solution (300 mL; slowly, a lot of effervescence was observed) and extracted with diethyl ether (2×300 mL). The combined organic layers were washed with brine (200 mL), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (eluant: 25-50% EtOAc/hexane) affording 3.76 g of 4-(4-(trifluoromethyl)phenyl)-tetrahydro-2H-pyran-4-carboxylic acid. MS m/e=275.1 (M+H)+.

Workup

temperaturethe reaction was warmed to 23° C
waitAfter 20 hours
extractionextracted with diethyl ether (2×300 mL)
washThe combined organic layers were washed with brine (200 mL)
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
custompurified by silica gel chromatography (eluant: 25-50% EtOAc/hexane)

Sources & evidence

ORD record: ord-b168cca92b784276a338ae1e4dbb1db7
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07635715B2

Reaction notes

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