Oxalyl chloride → Tert-butyl 2-(2-hydroxy-4-(trifluoromethyl)benzamido)ethylcarbamate

HRID 1027668Notes

Reaction equation

HRID 1027668 reaction equation
[OH:1][C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:21][CH2:22][CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28].C(N(C(C)C)CC)(C)C>C(Cl)Cl.CN(C=O)C>[OH:1][C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([NH:21][CH2:22][CH2:23][NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:6]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 1645782-Hydroxy-4-(trifluoromethyl)benzoic acidHCID 187201N-BOC-ethylenediamine

Product 1

HCID 67493387Tert-butyl 2-(2-hydroxy-4-(trifluoromethyl)benzamido)ethylcarbamateYield 65.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-hydroxy-4-(trifluoromethyl)benzoic acid (0.5 g, 2.4 mmol) in CH2Cl2 (8 mL0 was added oxalyl chloride (0.46 g, 3.6 mmol) and 2 drops of DMF. The reaction was stirred (RT, 2 h) and then concentrated. The resulting residue was dissolved in CH2Cl2 (8 mL) and tert-butyl 2-aminoethylcarbamate (0.39 g, 2.4 mmol) and diisopropylethylamine (0.41 g, 3.2 mmol) were added. The reaction was stirred (RT, 16 h) and then partitioned between CH2Cl2 and brine. The aqueous layer was extracted with CH2Cl2 and the combined organic extracts were dried over MgSO4. The crude material was purified by silica chromatography (0-10% MeOH/CH2Cl2) to afford 0.55 g of tert-butyl 2-(2-hydroxy-4-(trifluoromethyl)benzamido)ethylcarbamate. Mass calculated for C15H19F3N2O4=348.32. found: [M+Na]+=371.1. This was then dissolved in CH2Cl2 (10 mL) and TFA (4 mL). The reaction was stirred (RT, 3 h) and concentrated and dried to afford 0.7 g of N-(2-aminoethyl)-2-hydroxy-4-(trifluoromethyl)benzamide as a clear oil. Mass calculated for C10H11F3N2O2=248.20. found: [M+H]+=249.1.

Workup

  1. concentrationconcentrated
  2. dissolutionThe resulting residue was dissolved in CH2Cl2 (8 mL)
  3. stirringThe reaction was stirred (RT, 16 h)
  4. custompartitioned between CH2Cl2 and brine
  5. extractionThe aqueous layer was extracted with CH2Cl2
  6. dry with materialthe combined organic extracts were dried over MgSO4
  7. customThe crude material was purified by silica chromatography (0-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-4b2f4ab954e9431480240c663e3bb1f5
Source dataset
uspto-grants-2014_05
Patent number
US08735379B2

Reaction notes

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