Hydrochloric Acid → HCID 66796906, compound

HRID 1916888Notes

Reaction equation

HRID 1916888 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[NH:21])[C:10]([C:13]2[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:20])([CH3:12])[CH3:11])=[C:4]([F:22])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:30][C:31](=[O:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33].Cl>C1(C)C=CC=CC=1.C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:30][C:31]([OH:37])([C:32]([O:34][CH2:35][CH3:36])=[O:33])[N:21]=[C:9]2[C:10]([C:13]2[C:14]([Cl:20])=[CH:15][CH:16]=[CH:17][C:18]=2[Cl:19])([CH3:11])[CH3:12])=[C:4]([F:22])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 66144Ethyl bromopyruvateHCID 178449871HCID 178449871, compound

Product 1

HCID 66796906HCID 66796906, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a mixture of N-(4-bromo-2-fluorophenyl)-2-(2,6-dichlorophenyl)-2-methylpropanimidamide (48.0 g, 119 mmol), K2CO3 (41.0 g, 297 mmol) in toluene (180 mL) and THF (180 mL) at 55° C. was added slowly a solution of ethyl 3-bromo-2-oxopropanoate (23.3 mL, 166 mmol) in 24 mL of THF over 50 minutes. The reaction mixture was kept at 55° C. for 1.5 hours. A white slurry was observed. The reaction mixture was cooled to 5° C. HCl (0.5N, 450 mL) was added drop-wise (end point pH=9˜10). After addition, the suspension was cooled to 0° C. The solid was collected by filtration, washed with water (2×50 mL), and then dried in a vacuum oven at 60° C. overnight. Ethyl 1-(4-bromo-2-fluorophenyl)-2-(2-(2,6-dichlorophenyl)propan-2-yl)-4-hydroxy-4,5-dihydro-1H-imidazole-4-carboxylate (59 g, 114 mmol, 96% yield) was obtained as a white solid. 1H-NMR (CDCl3, 400 MHz) δ 7.11 (m, 3H), 6.96 (m, 2H), 6.72 (t, 1H, J=8.28 Hz), 4.35 (m, 2H), 4.25 (d, 1H, J=10.5 Hz), 3.80 (d, 1H, J=10.8 Hz), 1.98 (s, 3H), 1.93 (s, 3H), 1.38 (t, 3H, J=7.03 Hz); 13C-NMR (CDCl3, 126 MHz) δ 173.0, 171.5, 159.8, 157.8, 137.3, 135.7, 132.1, 131.1, 128.1, 127.4, 125.6, 122.2, 120.1, 93.5, 62.5, 45.5, 30.2, 14.0; MS m/e 517.05 (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): 2.74 minutes.

Workup

  1. additionAfter addition
  2. temperaturethe suspension was cooled to 0° C
  3. filtrationThe solid was collected by filtration
  4. washwashed with water (2×50 mL)
  5. customdried in a vacuum oven at 60° C. overnight

Sources & evidence

ORD record
ord-fe7bd9a48adc4288a84cae49116b6f75
Source dataset
uspto-grants-2013_12
Patent number
US08618154B2

Reaction notes

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