Cesium carbonate → HCID 88057141, compound

HRID 2122168Notes

Reaction equation

HRID 2122168 reaction equation
[F:1][C:2]([F:29])([O:6][C:7]1[CH:8]=[C:9]([CH2:13][N:14]([C:22]([OH:28])([CH3:27])[C:23]([F:26])([F:25])[F:24])C2C=C(O)C=CC=2)[CH:10]=[CH:11][CH:12]=1)[CH:3]([F:5])[F:4].Br[CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.[C:38](=[O:41])([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH:32]1([CH2:31][O:41][C:38]2[CH:11]=[C:12]([CH2:27][C:22]([NH:14][CH2:13][C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([O:6][C:2]([F:29])([F:1])[CH:3]([F:4])[F:5])[CH:8]=3)([OH:28])[C:23]([F:25])([F:24])[F:26])[CH:7]=[CH:8][CH:9]=2)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 137636Cyclohexane, (bromomethyl)-HCID 87792257HCID 87792257, compound

Product 1

HCID 88057141HCID 88057141, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](1,1,1-trifluoro-2-hydroxypropyl)-amino]phenol (100 mg, 0.23 mmol) and bromomethylcyclohexane (42 μL, 0.30 mmol) were dissolved in 2 mL of acetonitrile. Cesium carbonate (144 mg, 0.44 mmol) was added, and the stirred solution was warmed to 50° C. for 48 hours, at which time HPLC analysis indicated that no phenolic starting material remained. The reaction was quenched with water and filtered through pre-wetted celite eluting with ethyl acetate. The solvent was evaporated and the residue was purified by reverse phase HPLC eluting with 10% to 90% acetonitrile in water to afford 55 mg (35%) of the desired ether product as a brown oil, which was greater than 99% pure by reverse phase HPLC analysis. HRMS calcd. for C25H29F7NO3: 524.2036 [M+H]+, found: 524.2028. 1H NMR (CDCl3) δ0.9-1.4 (m, 5H), 1.7-1.9 (m, 6H), 3.6 (m, 3H), 3.9 (dd, 1H), 4.3 (m, 1H), 4.7 (m, 2H), 5.1 (s, 1H), 5.9 (tt, 1H), 6.5 (m, 3H), 7.0-7.4 (m, 5H).

Workup

  1. customThe reaction was quenched with water
  2. filtrationfiltered through pre-wetted
  3. washcelite eluting with ethyl acetate
  4. customThe solvent was evaporated
  5. customthe residue was purified by reverse phase HPLC
  6. washeluting with 10% to 90% acetonitrile in water
  7. customto afford 55 mg (35%) of the desired ether product as a brown oil, which

Sources & evidence

ORD record
ord-c897c3412d754605b23d8c48a60898be
Source dataset
uspto-grants-2004_02
Patent number
US06696472B2

Reaction notes

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