Triethylamine → HCID 68843970, compound

HRID 1723703Notes

Reaction equation

HRID 1723703 reaction equation
[CH3:1][O:2][C:3](=[O:18])[NH:4][C@@H:5]1[C@@H:9]([NH2:10])[CH2:8][N:7]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6]1.[F:19][C:20]([F:28])([CH2:26][Cl:27])[CH2:21][CH2:22][C:23](O)=[O:24].C(N(CC)CC)C>CCOC(C)=O>[CH3:1][O:2][C:3](=[O:18])[NH:4][C@@H:5]1[C@@H:9]([NH:10][C:23](=[O:24])[CH2:22][CH2:21][C:20]([F:28])([F:19])[CH2:26][Cl:27])[CH2:8][N:7]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 68840209HCID 68840209, compoundHCID 86617112HCID 86617112, compound

Product 1

HCID 68843970HCID 68843970, compoundYield 99.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent3×

Procedure

A solution of the product from Step 3 (2.20 g, 8.82 mmol), 4,4-difluoro-5-chloropentanoic acid (1.52 g, 8.82 mmol) and triethylamine (3.57 g, 35.3 mmol) in EtOAc (25 mL) was stirred as propanephosphonic acid cyclic anhydride (5.25 mL of a 50% solution of in EtOAc, 8.82 mmol) was added in one portion. After heating at reflux overnight, the reaction was cooled to room temperature, diluted with EtOAc (300 mL) and washed with saturated sodium carbonate solution. The organic layer was dried over sodium sulfate and concentrated to an oil that was separated by silica gel chromatography (Biotage 25+S (A Dynax Corp.; Charlottesville, Va.) eluting with a dichloromethane/methanol/ammonium hydroxide gradient (100:0:0-95:5:0.25). The desired fractions were concentrated and triturated with di-isopropylether to afford 3.56 g (70%) of the product as a white solid. 1H NMR (400 MHz, Chloroform-d) δ 7.36-7.22 (m, 5H), 6.14-6.00 (br s, 1H), 5.17-5.04 (br s, 1H), 4.17-4.04 (br m, 1H), 4.00-3.86 (br m, 1H), 3.74-3.49 (m, 4H), 3.65 and 3.63 (s, 3H), 3.12-2.94 (m, 2H), 2.49-2.43 (m, 1H), 2.42-2.49 (m, 4H). MS 404.2 (AP+, 100).

Workup

  1. additionwas added in one portion
  2. temperatureAfter heating
  3. temperatureat reflux overnight
  4. washwashed with saturated sodium carbonate solution
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated to an oil that
  7. customwas separated by silica gel chromatography (Biotage 25+S (A Dynax Corp
  8. wash) eluting with a dichloromethane/methanol/ammonium hydroxide gradient (100:0:0-95:5:0.25)
  9. concentrationThe desired fractions were concentrated
  10. customtriturated with di-isopropylether

Sources & evidence

ORD record
ord-c25946e752124b67bdefe782c1b3230b
Source dataset
uspto-grants-2009_02
Patent number
US07485641B2

Reaction notes

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