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

HRID 1839958Notes

Reaction equation

HRID 1839958 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), 4.45-4.50 (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-09415f75098e49df8a84ab453bd15d5a
Source dataset
uspto-grants-2004_01
Patent number
US06677382B1

Reaction notes

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