Hydrochloric Acid → 4-(Adamantan-1-ylmethoxy)-5-bromo-2-fluorobenzoic acid

HRID 1849746Notes

Reaction equation

HRID 1849746 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.CC(C)([O-])C.[K+].[Br:19][C:20]1[C:21](F)=[CH:22][C:23]([F:29])=[C:24]([CH:28]=1)[C:25]([OH:27])=[O:26].Cl.BrC1C(F)=CC=C(C=1)C(O)=O>CS(C)=O.O>[C:1]12([CH2:11][O:12][C:21]3[C:20]([Br:19])=[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

8

Reactant 5

HCID 313Hydrochloric AcidHCID 64556Tricyclo(3.3.1.1'3,7)dec-1-ylmethanolHCID 705093-Bromo-4-fluorobenzoic acidHCID 111607285-Bromo-2,4-difluorobenzoic acidHCID 23665647Potassium tert-butoxide

Product 1

HCID 867036284-(Adamantan-1-ylmethoxy)-5-bromo-2-fluorobenzoic acid

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

A mixture of adamantan-1-ylmethanol (3.51 g, 21.10 mmol) and potassium tert-butoxide (5.45 g, 48.5 mmol) in anhydrous dimethylsulfoxide (125 mL) was stirred for 20 minutes. To the reaction mixture was then added 5-bromo-2,4-difluorobenzoic acid (5.00 g, 21.10 mmol) followed by anhydrous dimethylsulfoxide (25 mL). The resulting mixture was stirred for 18 hours at ambient temperature. The reaction mixture was diluted with water (300 mL), and adjusted to pH 3 with 3 M hydrochloric acid. The obtained solid was filtered off and rinsed with water (200 mL) to provide a 2:1 mixture of the title compound and 2-adamantan-1-ylmethoxy)-5-bromo-4-fluorobenzoic acid (6.97 g, 86%). Major isomer: 1H NMR (300 MHz, DMSO-d6) δ 7.94 (d, J=7.9 Hz, 1H), 7.05 (d, J=12.9 Hz, 1H), 3.65 (s, 2H), 1.98-1.83 (m, 3H), 1.72-1.48 (m, 12H); MS (ES−) m/z 381.13, 383.12 (M−1).

Workup

  1. stirringThe resulting mixture was stirred for 18 hours at ambient temperature
  2. filtrationThe obtained solid was filtered off
  3. washrinsed with water (200 mL)
  4. customto provide

Sources & evidence

ORD record
ord-da83b631b87e447d99a9e5edfdc89df5
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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