Dichloromethane → 5-(3,3-Difluoropyrrolidine-1-carbonyl)-N-methyl-N-propyl-isophthalamic acid ethyl ester

HRID 1436645Notes

Reaction equation

HRID 1436645 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:13]=[C:12]([C:14](=[O:20])[N:15]([CH3:19])[CH2:16][CH2:17][CH3:18])[CH:11]=[C:7]([C:8](O)=[O:9])[CH:6]=1)[CH3:2].ClCCl.Cl.[F:26][C:27]1([F:32])[CH2:31][CH2:30][NH:29][CH2:28]1.C(N(CC)CC)C>ON1C2C=CC=CC=2N=N1.C(O)(C)(C)C.C(OCC)(=O)C.C(#N)C>[CH2:1]([O:3][C:4](=[O:21])[C:5]1[CH:6]=[C:7]([C:8]([N:29]2[CH2:30][CH2:31][C:27]([F:32])([F:26])[CH2:28]2)=[O:9])[CH:11]=[C:12]([C:14]([N:15]([CH3:19])[CH2:16][CH2:17][CH3:18])=[O:20])[CH:13]=1)[CH3:2]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 249034823,3-Difluoropyrrolidine hydrochlorideHCID 688146805-(Methyl-propylcarbamoyl)-isophthalic acid monoethyl ester

Product 1

HCID 688143585-(3,3-Difluoropyrrolidine-1-carbonyl)-N-methyl-N-propyl-isophthalamic acid ethyl esterYield 31%

Reagents, catalysts & solvents 4

HCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolventHCID 757711-HydroxybenzotriazoleSolvent

Procedure

Dissolve 5-(methyl-propylcarbamoyl)-isophthalic acid monoethyl ester (667 mg, 2.3 mmol) in a 0.1 N 1-hydroxybenzotriazole solution of 1:1:5 tert-butanol:acetonitrile:dichloromethane (23 mL, 2.3 mmol). Stir the solution at room temperature for 5 min, add 3,3-difluoropyrrolidine hydrochloride (331 mg, 2.3 mmol) and triethylamine (640 μL, 4.6 mmol). Stir the reaction at room temperature for 2 h, add ethyl acetate (100 mL) and wash with saturated aqueous ammonium chloride (2×30 mL), saturated aqueous sodium chloride (30 mL), dry (sodium sulfate), concentrate and purify (silica gel chromatography, eluting with 50:50 ethyl acetate:hexanes) to give the title compound (270 mg, 31%).

Workup

  1. stirringStir
  2. customthe reaction at room temperature for 2 h
  3. washwash with saturated aqueous ammonium chloride (2×30 mL), saturated aqueous sodium chloride (30 mL)
  4. dry with materialdry (sodium sulfate)
  5. concentrationconcentrate
  6. custompurify
  7. wash(silica gel chromatography, eluting with 50:50 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-b63f5e01ea74462aa47e50ede7a53397
Source dataset
uspto-grants-2009_11
Patent number
US07618978B2

Reaction notes

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