Sodium Hydroxide → (4-chloro-2-fluoro-9-trifluoromethyl-9H-fluoren-9-yloxy)-acetic acid

HRID 541117Notes

Reaction equation

C([O:3][C:4](=[O:26])[CH2:5][O:6][C:7]1([C:22]([F:25])([F:24])[F:23])[C:19]2[CH:18]=[C:17]([F:20])[CH:16]=[C:15]([Cl:21])[C:14]=2[C:13]2[C:8]1=[CH:9][CH:10]=[CH:11][CH:12]=2)C.[OH-].[Na+]>C(O)C>[Cl:21][C:15]1[C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]([C:22]([F:23])([F:24])[F:25])([O:6][CH2:5][C:4]([OH:26])=[O:3])[C:19]=2[CH:18]=[C:17]([F:20])[CH:16]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of ethanol (440 ml) and (4-chloro-2-fluoro-9-trifluoromethyl-9H-fluoren-9-yloxy)-acetic acid ethyl ester (360 g) was added 2N aqueous sodium hydroxide solution (877 ml), and the mixture was stirred at 80° C. for 3.5 hr. The reaction mixture was cooled to room temperature, insoluble material was filtered off through celite, and washed with water (500 ml) and ethanol (60 ml). Water (120 ml) was added to the filtrate and the mixture was ice-cooled, and formic acid (199 ml) was added dropwise. This suspension was stirred at room temperature overnight, and filtered. The obtained solid was washed with 25 v/v % ethanol-water (400 ml), air-dried overnight, and dried under reduced pressure at 60° C. to give the title compound (285 g, 2 steps 90%).

Workup

temperatureThe reaction mixture was cooled to room temperature
filtrationinsoluble material was filtered off through celite
washwashed with water (500 ml) and ethanol (60 ml)
additionWater (120 ml) was added to the filtrate
temperaturecooled
additionformic acid (199 ml) was added dropwise
stirringThis suspension was stirred at room temperature overnight
filtrationfiltered
washThe obtained solid was washed with 25 v/v % ethanol-water (400 ml)
customair-dried overnight
customdried under reduced pressure at 60° C.

Sources & evidence

ORD record: ord-e14e918a745147cc9545dbb0e361bc3f
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871934B2

Reaction notes

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