Triethylamine → Methyl 1-{[(5-bromo-2-methylphenyl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

HRID 1841891Notes

Reaction equation

HRID 1841891 reaction equation
S(Cl)(Cl)=O.[Br:5][C:6]1[CH:7]=[CH:8][C:9]([CH3:16])=[C:10]([CH2:12][C:13]([OH:15])=O)[CH:11]=1.Cl.[NH2:18][C:19]1([C:27]([O:29][CH3:30])=[O:28])[CH2:24][CH2:23][C:22]([F:26])([F:25])[CH2:21][CH2:20]1.C(N(CC)CC)C>O1CCCC1>[Br:5][C:6]1[CH:7]=[CH:8][C:9]([CH3:16])=[C:10]([CH2:12][C:13]([NH:18][C:19]2([C:27]([O:29][CH3:30])=[O:28])[CH2:24][CH2:23][C:22]([F:26])([F:25])[CH2:21][CH2:20]2)=[O:15])[CH:11]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 510637432-(5-Bromo-2-methylphenyl)acetic acidHCID 60196672Methyl 1-amino-4,4-difluorocyclohexanecarboxylate hydrochloride

Product 1

HCID 68282721Methyl 1-{[(5-bromo-2-methylphenyl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

36.5 ml (500 mmol) of thionyl chloride were added to 22.91 g (100 mmol) of (5-bromo-2-methylphenyl)acetic acid (EP 1791816 A1 and WO 2006/29799 A1), and the mixture was stirred at 80° C. until the evolution of gas was complete and then concentrated. The residue was dissolved in 100 ml of tetrahydrofuran (THF) (solution A). 25.3 g (110 mmol) of the compound from Example 4A were initially charged in 308 ml of THF, 21.3 ml of triethylamine were added dropwise at 20° C., solution A was then added dropwise with cooling and the mixture was stirred at room temperature until the reaction had gone to completion. The precipitate is filtered off with suction and washed with THF, the filtrate is concentrated under reduced pressure and the residue is recrystallized from methyl tert-butyl ether. This gave 33.6 g (83% of theory) of the title compound.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in 100 ml of tetrahydrofuran (THF) (solution A)
  3. temperaturewith cooling
  4. stirringthe mixture was stirred at room temperature until the reaction
  5. filtrationThe precipitate is filtered off with suction
  6. washwashed with THF
  7. concentrationthe filtrate is concentrated under reduced pressure
  8. customthe residue is recrystallized from methyl tert-butyl ether

Sources & evidence

ORD record
ord-8a485ef6fc7e40109af79fed3c71a506
Source dataset
uspto-grants-2015_02
Patent number
US08946124B2

Reaction notes

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