Citric Acid → N-[4-(3-Fluoro-phenoxymethyl)-phenyl]-malonamic Acid Methyl Ester

HRID 1827387Notes

Reaction equation

HRID 1827387 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1.C(N(CC)CC)C.C[CH:25]([C:29](Cl)=[O:30])[C:26](Cl)=[O:27].C(O)(=O)C[C:34](CC(O)=O)(C(O)=O)[OH:35]>ClCCl.O>[CH3:34][O:35][C:29](=[O:30])[CH2:25][C:26]([NH:13][C:10]1[CH:9]=[CH:8][C:7]([CH2:6][O:5][C:4]2[CH:14]=[CH:15][CH:16]=[C:2]([F:1])[CH:3]=2)=[CH:12][CH:11]=1)=[O:27]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 8471TriethylamineHCID 10931669MethylmalonylchlorideHCID 167938064-(3-Fluoro-phenoxymethyl)-phenylamine

Product 1

HCID 69006710N-[4-(3-Fluoro-phenoxymethyl)-phenyl]-malonamic Acid Methyl EsterYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

211 mg (1 mmol) of the crude 4-(3-fluoro-phenoxymethyl)-phenylamine is dissolved in 3 ml dichloromethane. 110 mg (1.1 mmol) of triethylamine is added and the reaction mixture cooled in an ice-bath 132 mg (1 mmol) of methyl malonyl chloride is then added dropwise. The reaction mixture is stirred for additional 30 minutes in the ice-bath, then for 45 minutes at room temperature. The reaction mixture is treated with water, acidified with citric acid and extracted 3 times with dichloromethane. The organic phase is dried and evaporated. Chromatography (silica gel, ethyl acetate/hexane 1:1) yields 98 mg (32%) of the title compound as a colorless solid. MS: m/e=318.2 (M++H).

Workup

  1. additionis then added dropwise
  2. extractionextracted 3 times with dichloromethane
  3. customThe organic phase is dried
  4. customevaporated

Sources & evidence

ORD record
ord-86b45364711b48c582f8280e0b33091f
Source dataset
uspto-grants-2006_05
Patent number
US07053245B2

Reaction notes

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