Hydrochloric Acid → 3-[[3-[[[3-(1,1,2,2-Tetrafluoroethoxy)phenyl]methyl](3,3,3-trifluoro-2-hydroxypropyl)amino]phenoxy]methyl]benzoic acid

HRID 1840070Notes

Reaction equation

HRID 1840070 reaction equation
[F:1][C:2]([F:41])([O:6][C:7]1[CH:8]=[C:9]([CH2:13][N:14]([CH2:34][CH:35]([OH:40])[C:36]([F:39])([F:38])[F:37])[C:15]2[CH:16]=[C:17]([CH:31]=[CH:32][CH:33]=2)[O:18][CH2:19][C:20]2[CH:21]=[C:22]([CH:28]=[CH:29][CH:30]=2)[C:23]([O:25]CC)=[O:24])[CH:10]=[CH:11][CH:12]=1)[CH:3]([F:5])[F:4].[OH-].[Li+].Cl>O.O1CCCC1>[F:1][C:2]([F:41])([O:6][C:7]1[CH:8]=[C:9]([CH2:13][N:14]([CH2:34][CH:35]([OH:40])[C:36]([F:37])([F:38])[F:39])[C:15]2[CH:16]=[C:17]([CH:31]=[CH:32][CH:33]=2)[O:18][CH2:19][C:20]2[CH:21]=[C:22]([CH:28]=[CH:29][CH:30]=2)[C:23]([OH:25])=[O:24])[CH:10]=[CH:11][CH:12]=1)[CH:3]([F:4])[F:5]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 23506059Ethyl 3-[[3-[[[3-(1,1,2,2-tetrafluoroethoxy) phenyl]methyl]-(3,3,3-trifluoro-2-hydroxypropyl)amino]phenoxy]methyl]benzoate

Product 1

HCID 235060493-[[3-[[[3-(1,1,2,2-Tetrafluoroethoxy)phenyl]methyl](3,3,3-trifluoro-2-hydroxypropyl)amino]phenoxy]methyl]benzoic acidYield 24.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

EX-435A) A solution of ethyl 3-[[3-[[[3-(1,1,2,2-tetrafluoroethoxy) phenyl]methyl]-(3,3,3-trifluoro-2-hydroxypropyl)amino]phenoxy]methyl]benzoate (22.1 mg, 0.04 mmol) and lithium hydroxide (5 mg, 0.12 mmol) in water (1 mL) and tetrahydrofuran (0.5 mL) was heated at 80° C. for 16 h. The reaction mixture was added to 6 N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was evaporated. The residue was purified by reverse phase HPLC eluting with 10% to 90% acetonitrile in water to afford 5.6 mg (19%) of the desired benzoic acid product as a brown oil. HRMS calcd. for C26H23F7NO5: 562.1464 [M+H]+, found: 562.1418. 1H NMR (acetone-d6) δ 3.64 (dd, 1H), 3.95 (m, 1H), 4.454.50 (m, 1H), 4.80 (s, 2H), 5.12 (s, 2H), 6.27-6.63 (m, 4H), 7.06-7.27 (m, 4H), 7.41 (t, 1H), 7.50 (t, 1H), 7.66 (d, 1H), 7.99 (d, 1H), 8.10 (s, 1H).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. customthe solvent was evaporated
  4. customThe residue was purified by reverse phase HPLC
  5. washeluting with 10% to 90% acetonitrile in water

Sources & evidence

ORD record
ord-b1164fa535e5438d84ea15d60175105c
Source dataset
uspto-grants-2004_01
Patent number
US06677353B2

Reaction notes

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