1-Aminocyclopropane-1-carboxylic acid → HCID 53492644, compound

HRID 1800957Notes

Reaction equation

HRID 1800957 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]2[C:17]([CH3:19])([CH3:18])[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:20]([OH:22])=[O:21])[CH:14]=3)[NH:9]2)[CH:5]=[CH:6][CH:7]=1.[NH2:23][C:24]1([C:27]([OH:29])=[O:28])[CH2:26][CH2:25]1.Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[C:27]([C:24]1([NH:23][C:2]2[CH:3]=[C:4]([CH:8]3[C:17]([CH3:19])([CH3:18])[CH2:16][C:15]4[C:10](=[CH:11][CH:12]=[C:13]([C:20]([OH:22])=[O:21])[CH:14]=4)[NH:9]3)[CH:5]=[CH:6][CH:7]=2)[CH2:26][CH2:25]1)([OH:29])=[O:28]

Participants

7

Reactant 4

HCID 5351-Aminocyclopropane-1-carboxylic acidHCID 11430Potassium CarbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 584761942-(3-Bromophenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylic acid

Product 1

HCID 53492644HCID 53492644, compoundYield 77.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-(3-bromo-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (500 mg, 1.39 mmol), 1-amino-cyclopropanecarboxylic acid (700 mg, 6.95 mmol), copper(I) iodide (159 mg, 0.85 mmol), N,N-dimethylglycine hydrochloride (155 g, 1.11 mmol) and potassium carbonate (577 mg, 4.17 mmol) in dimethyl sulfoxide (5 mL) was stirred at 120° C. for 12 h. Then the reaction mixture cooled to room temperature. The reaction mixture was extracted with ethyl acetate (2×150 mL), washed with water (2×50 mL) and saturated aqueous ammonium chloride solution (2×50 mL), dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% formic acid in water) afforded 2-[3-(1-carboxy-cyclopropylamino)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (410 mg, 77%) as a white solid: LC/MS m/e calcd for C22H24N2O4 (M+H)+: 381.45, observed: 381.2.

Workup

  1. temperatureThen the reaction mixture cooled to room temperature
  2. extractionThe reaction mixture was extracted with ethyl acetate (2×150 mL)
  3. washwashed with water (2×50 mL) and saturated aqueous ammonium chloride solution (2×50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% formic acid in water)

Sources & evidence

ORD record
ord-7b6afc2c652244f9b2a37b6b667eae22
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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