Triethylamine → 4-fluoro-N-[3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3,3,3-trifluoro-2-hydroxypropyl)amino]-phenyl]benzamide

HRID 48040Notes

Reaction equation

HRID 48040 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([N:8]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:18]=2)[CH2:9][CH:10]([OH:15])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[F:37][C:38]1[CH:46]=[CH:45][C:41]([C:42](Cl)=[O:43])=[CH:40][CH:39]=1>ClCCl>[F:37][C:38]1[CH:46]=[CH:45][C:41]([C:42]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([N:8]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]([F:28])([F:29])[CH:25]([F:26])[F:27])[CH:18]=3)[CH2:9][CH:10]([OH:15])[C:11]([F:14])([F:13])[F:12])[CH:3]=2)=[O:43])=[CH:40][CH:39]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 678794-Fluorobenzoyl chlorideHCID 235060463-[(3-Aminophenyl)[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

Product 1

HCID 235060124-fluoro-N-[3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3,3,3-trifluoro-2-hydroxypropyl)amino]-phenyl]benzamideYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-[(3-aminophenyl)[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol (50 mg, 0.12 mmol) was dissolved in 1 mL of dichloromethane. Triethylamine (25 μL, 0.18 mmol) followed by 4-fluorobenzoyl chloride were added. The solution was stirred at room temperature for 5 hours, at which time HPLC analysis indicated that no 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 15 mg (23%) of the desired 4-fluoro-N-[3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl](3,3,3-trifluoro-2-hydroxypropyl)amino]-phenyl]benzamide product as a yellow oil, which was greater than 98% pure by reverse phase HPLC analysis. HRMS calcd. for C25H21F8N2O3: 549.1424 [M+H]+, found: 549.1436. 1H NMR (CDCl3) δ3.6 (dd, 1H), 3.8 (dd, 1H), 4.4 (m, 1H), 4.6 (s, 2H), 5.9 (tt, 1H), 6.6 (d, 1H), 6.8 (d, 1H), 7.0-7.4 (m, 7H), 7.8 (m, 3H).

Workup

  1. additionwere added
  2. customThe reaction was quenched with water
  3. filtrationfiltered through pre-wetted
  4. washcelite eluting with ethyl acetate
  5. customThe solvent was evaporated
  6. customthe residue was purified by reverse phase HPLC
  7. washeluting with 10% to 90% acetonitrile in water

Sources & evidence

ORD record
ord-cb750d571204483c99baf39a5dcfad8a
Source dataset
uspto-grants-2004_03
Patent number
US06699898B2

Reaction notes

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