Diisopropylethylamine → HCID 11696413, compound

HRID 347898Notes

Reaction equation

HRID 347898 reaction equation
Cl.[NH2:2][C:3]1[CH:4]=[C:5]([CH:16]=[C:17]([F:19])[CH:18]=1)[O:6][C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:15])[CH3:14])[CH2:8]1.CCN(C(C)C)C(C)C.[N:29]([C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)=[C:30]=[O:31].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CO.ClCCl>[C:13]([N:9]1[CH2:10][CH2:11][CH2:12][C@@H:7]([O:6][C:5]2[CH:4]=[C:3]([NH:2][C:30]([NH:29][C:32]3[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=3)=[O:31])[CH:18]=[C:17]([F:19])[CH:16]=2)[CH2:8]1)(=[O:15])[CH3:14]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27604933-Isocyanatopyridine2×HCID 68983099HCID 68983099, compound

Product 1

HCID 11696413HCID 11696413, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

A 22 L 3-neck RBF equipped with a cooling bath, mechanical stirrer, thermocouple, and nitrogen bubbler was purged with nitrogen for at least ten minutes. The flask was charged with 1.441 kg (4.990 mol) 1-[(R)-3-(3-amino-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone HCl salt and 14.4 L (10 vol) dichloromethane. The solution was stirred, and 0.710 kg (5.489 mol) DIPEA was charged. The solution was cooled to 10±5° C. in an ice/brine bath. The reaction was charged with 0.659 kg (5.489 mol) 3-isocyanato-pyridine and the solution warmed to room temperature and stirred for three hours. The reaction was monitored by TLC (1:9 methanol:ethyl acetate/PMA stain) and HPLC. The reaction stirred at room temperature for five more hours, and another 0.009 kg (0.075 mol) 3-isocyanato-pyridine was added. The solution stirred for 15 more hours, and the reaction was deemed complete. The solution was poured into a 50 L extractor containing 14.4 L (10 vol) saturated sodium bicarbonate, and the flask was rinsed with an additional 1.44 L (1 vol) dichloromethane. The layers were separated, and the organic layer was washed with 14.4 L (2×10 vol) water. The organic layer was dried with 1.69 kg sodium sulfate for at least 20 minutes before proceeding to the next step.

Workup

  1. customA 22 L 3-neck RBF equipped with a cooling bath, mechanical stirrer
  2. customthermocouple, and nitrogen bubbler was purged with nitrogen for at least ten minutes
  3. temperaturethe solution warmed to room temperature
  4. stirringstirred for three hours
  5. stirringThe reaction stirred at room temperature for five more hours
  6. stirringThe solution stirred for 15 more hours
  7. additionThe solution was poured into a 50 L extractor
  8. washthe flask was rinsed with an additional 1.44 L (1 vol) dichloromethane
  9. customThe layers were separated
  10. washthe organic layer was washed with 14.4 L (2×10 vol) water
  11. dry with materialThe organic layer was dried with 1.69 kg sodium sulfate for at least 20 minutes

Sources & evidence

ORD record
ord-c302b048e30b4883b2cbdf9efdfe8eff
Source dataset
uspto-grants-2007_02
Patent number
US07176222B2

Reaction notes

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