Hydrochloric Acid → 4-(Adamantan-1-ylmethoxy)-2-fluoro-5-methylbenzoic acid

HRID 1427883Notes

Reaction equation

HRID 1427883 reaction equation
[C:1]12([CH2:11][OH:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH3:13]C(C)([O-])C.[K+].Cl[C:20]1[C:21](F)=[CH:22][C:23]([F:29])=[C:24]([CH:28]=1)[C:25]([OH:27])=[O:26].Cl.[Cl-].[NH4+]>CS(C)=O>[C:1]12([CH2:11][O:12][C:21]3[C:20]([CH3:13])=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[C:23]([F:29])[CH:22]=3)[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 64556Tricyclo(3.3.1.1'3,7)dec-1-ylmethanolHCID 148764175-Chloro-2,4-difluorobenzoic acidHCID 23665647Potassium tert-butoxide

Product 1

HCID 867029084-(Adamantan-1-ylmethoxy)-2-fluoro-5-methylbenzoic acid

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 1-adamantane methanol (2.40 g, 14.40 mmol) in anhydrous dimethylsulfoxide (20 ml) was added potassium tert-butoxide (4.86 g, 43.30 mmol) and the suspension was stirred at ambient temperature for 30 min. 5-chloro-2,4-difluorobenzoic acid (2.50 g, 14.40 mmol) was added to the reaction mixture and stirred at 50° C. for 72 h. The reaction mixture was acidified to pH=1 with cold aqueous hydrochloric acid solution (1N), followed by addition of 25% aqueous ammonium chloride solution (200 mL). The solid was collected by filtration and washed with water and a mixture of hexanes/diethyl ether (3/1, v/v). Recrystallization of the crude product from ethyl acetate and hexanes to afford the title compound as a beige color solid (0.77 g, 17%): MS (ES+) m/z 437.2 (M+1).

Workup

  1. stirringstirred at 50° C. for 72 h
  2. filtrationThe solid was collected by filtration
  3. washwashed with water
  4. additiona mixture of hexanes/diethyl ether (3/1
  5. customRecrystallization of the crude product from ethyl acetate and hexanes

Sources & evidence

ORD record
ord-abe46f8554f041a280fc845e6ea0928d
Source dataset
uspto-grants-2015_01
Patent number
US08933236B2

Reaction notes

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