Triethylamine → HCID 57539235, compound

HRID 601963Notes

Reaction equation

HRID 601963 reaction equation
[CH2:1]([N:8]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH:9]([CH2:13][O:14][CH:15]([F:17])[F:16])[C:10]([OH:12])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[F:40][C:41]1[CH:42]=[C:43]([CH:46]=[CH:47][C:48]=1[F:49])[CH2:44][NH2:45]>C1COCC1.C(OCC)(=O)C>[CH2:18]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH:9]([CH2:13][O:14][CH:15]([F:16])[F:17])[C:10]([NH:45][CH2:44][C:43]1[CH:46]=[CH:47][C:48]([F:49])=[C:41]([F:40])[CH:42]=1)=[O:12])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 1235723,4-DifluorobenzylamineHCID 57539219HCID 57539219, compound

Product 1

HCID 57539235HCID 57539235, compoundYield 77.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(dibenzylamino)-3-(difluoromethoxy)propanoic acid (280 mg, 0.835 mmol) and triethylamine (338 mg, 3.34 mmol) in THF (5 mL) at −5° C., isobutyl chloroformate (119.8 mg, 0.876 mmol) was added dropwise. After 20 minutes, 3,4-difluorobenzylamine (131.3 mg, 0.919 mmol) was added and the reaction mixture allowed to warm up to 0° C. for another hour. The mixture was then diluted with ethyl acetate and washed with water, 0.5 N HCl and Brine. The organic layer was dried over magnesium sulphate, concentrated with silica gel and purified by column chromatography, eluting with 10˜20% ethyl acetate in hexanes, to give 2-dibenzylamino-N-(3,4-difluoro-benzyl)-3-difluoromethoxy-propionamide (298 mg, 77.5%) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ(ppm) 7.56 (t, 1H), 6.82-7.38 (m, 13H), 6.60 (wt, 1H), 4.58 (dd, 1H), 4.37 (m, 3H), 3.90 (d, 2H), 3.73 (d, 2H) and 3.70 (m, 1H).

Workup

  1. washwashed with water, 0.5 N HCl and Brine
  2. dry with materialThe organic layer was dried over magnesium sulphate
  3. concentrationconcentrated with silica gel
  4. custompurified by column chromatography
  5. washeluting with 10˜20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-4acc820c89754b23a316ab4ec029353e
Source dataset
uspto-grants-2011_03
Patent number
US07902401B2

Reaction notes

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