(alpha,alpha,alpha-Trifluoro-4-tolyl)acetic acid → HCID 22141171, compound

HRID 1826486Notes

Reaction equation

HRID 1826486 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1.O.O[N:17]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:38][C:39]1([C:45]2[CH:46]=[C:47]([NH:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH:48]=[CH:49][CH:50]=2)[CH:44]2[CH:40]1[CH2:41][NH:42][CH2:43]2.C(=O)([O-])O.[Na+]>CN(C)C=O>[NH3:17].[CH3:38][C:39]1([C:45]2[CH:46]=[C:47]([NH:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH:48]=[CH:49][CH:50]=2)[CH:44]2[CH:40]1[CH2:41][N:42]([C:10](=[O:12])[CH2:9][C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:14])[F:13])=[CH:8][CH:7]=1)[CH2:43]2

Participants

8

Reactant 5

HCID 118342(alpha,alpha,alpha-Trifluoro-4-tolyl)acetic acidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamide

Product 2

HCID 222AmmoniaHCID 22141171HCID 22141171, compoundYield 49.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(trifluoromethyl)phenyl acetic acid (63 mg, 0.31 mmol) in N,N-dimethylformamide (6.5 ml) was added 1-hydroxybenzotriazole monohydrate (50 mg, 0.33 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (85 mg, 0.44 mmol). After stirring at room temperature for 5 min the mixture was treated with the hydrochloride salt of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide (Preparation 53, 100 mg, 0.33 mmol) and sodium hydrogen carbonate (28 mg, 0.34 mmol). The reaction mixture was stirred at room temperature for 18 h before concentrating in vacuo. Water (10 ml) was added and the reaction mixture was extracted with ethyl acetate (2×15 ml). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to give a light brown oil. The residue was purified by chromatography using a Sep-Pak™ cartridge packed with silica gel (5 g) eluting with dichloromethane:ethanol:0.88 ammonia (200:8:1) to afford the title compound as a glassy oil (70 mg, 47%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 18 h
  2. concentrationbefore concentrating in vacuo
  3. additionWater (10 ml) was added
  4. extractionthe reaction mixture was extracted with ethyl acetate (2×15 ml)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a light brown oil
  9. customThe residue was purified by chromatography
  10. washeluting with dichloromethane

Sources & evidence

ORD record
ord-1536338899be47329f22d29af5bef8d9
Source dataset
uspto-grants-2006_05
Patent number
US07049444B2

Reaction notes

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