Trifluoroacetic acid → HCID 66796747, compound

HRID 1916889Notes

Reaction equation

HRID 1916889 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][C:11](O)([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:10]=[C:9]2[C:19]([C:22]2[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=2[Cl:29])([CH3:21])[CH3:20])=[C:4]([F:30])[CH:3]=1.C(O)(C(F)(F)F)=O.[OH-].[Na+]>CCO.C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:10]=[C:9]2[C:19]([C:22]2[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:23]=2[Cl:29])([CH3:20])[CH3:21])=[C:4]([F:30])[CH:3]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 66796906HCID 66796906, compound

Product 1

HCID 66796747HCID 66796747, compoundYield 87.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
95 °C

Procedure

To a mixture of ethyl 1-(4-bromo-2-fluorophenyl)-2-(2-(2,6-dichlorophenyl)propan-2-yl)-4-hydroxy-4,5-dihydro-1H-imidazole-4-carboxylate (38 g, 73 mmol) in EtOH (200 mL) was added TFA (25.0 g, 220 mmol). The mixture was subsequently heated to 95° C. HPLC analysis after 2.5 hours showed <1% of alcohol intermediate remaining The mixture was diluted with 300 mL of CH2Cl2 and cooled to approximately 5° C. with an ice bath. The mixture was neutralized with 1N NaOH (120 mL) and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (2×100 mL). The combined organic layers were concentrated on a rotary evaporator to give crude material. Recrystallization in EtOH (5 mL/1 g) provided 32 g of ethyl 1-(4-bromo-2-fluorophenyl)-2-(2-(2,6-dichlorophenyl)propan-2-yl)-1H-imidazole-4-carboxylate as an off-white solid (86% yield). 1H-NMR (DMSO-d6, 400 MHz) δ 7.92 (s, 1H), 7.16 (d, 1H, J=8.0 Hz), 7.22 (m, 3H), 7.11 (m, 1H), 7.04 (t, 1H, J=12.0 Hz), 4.25 (q, 2H, J=8.0 Hz), 1.94 (s, 6H), 1.27 (t, 3H, J=8.0 Hz); MS m/e 502.68 (M+H+); HPLC (XBridge 5μ C18 4.6×50 mm, 4 mL/min, Solvent A: 10% MeOH/water with 0.2% H3PO4, Solvent B: 90% MeOH/water with 0.2% H3PO4, gradient with 0-100% B over 4 minutes): 3.87 minutes.

Workup

  1. temperaturecooled to approximately 5° C. with an ice bath
  2. customthe organic layer was separated
  3. extractionThe aqueous layer was extracted with CH2Cl2 (2×100 mL)
  4. concentrationThe combined organic layers were concentrated on a rotary evaporator
  5. customto give crude material
  6. customRecrystallization in EtOH (5 mL/1 g)

Sources & evidence

ORD record
ord-d8e1409bd6ea4d79aee208e0dfe7e226
Source dataset
uspto-grants-2013_12
Patent number
US08618154B2

Reaction notes

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