Dichloromethane → N-((3S,4R)-1-ethyl-3-fluoropiperidin-4-yl)benzamide

HRID 1257566Notes

Reaction equation

HRID 1257566 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][C:6]([NH:9][C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:5]([F:18])[CH2:4]1)[CH3:2].ClCCl.[H][H]>CO>[CH2:1]([N:3]1[CH2:8][CH2:7][C@@H:6]([NH:9][C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@@H:5]([F:18])[CH2:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 56954900N-(1-ethyl-3-fluoro-1,2,5,6-tetrahydro-pyridin-4-yl)benzamideHCID 178418361HCID 178418361, compound

Product 1

HCID 56954901N-((3S,4R)-1-ethyl-3-fluoropiperidin-4-yl)benzamideYield 108.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

A 50 L autoclave was purged with nitrogen. N-(1-ethyl-3-fluoro-1,2,5,6-tetrahydro-pyridin-4-yl)benzamide (6.00 kg, 24.16 mol) was dissolved in methanol (19 L) and dichloromethane (1 L) and transferred to the inert autoclave. After four high vacuum—nitrogen fill cycles the prepared catalyst solution (6.5 L) was added to the autoclave. The reaction was pressurized with hydrogen gas to 20 bar and left to stand at 1000 rpm for 20 h at room temperature, was heated to 40° C. for 7 h, and then cooled to 25° C. Following a nitrogen purge the contents of autoclave were transferred into a 60 L reactor with methanol (2.0 L). Deloxan THPII (2.4 kg, 40 mass %) was added, and stirred at 500 rpm for 3 days at room temperature. The suspension was filtered over Arbocel (0.7 kg) applying high vacuum, the filter cake was washed with methanol (5.0 L), and solvent evaporated at 20 mbar and 45° C. Obtained 6.58 kg of N-((3S,4R)-1-ethyl-3-fluoropiperidin-4-yl)benzamide which was used without further purification. 1H NMR (400 MHz, MeOD) δ 7.83 (2H, t, J=9.1 Hz), 7.53 (1H, t, J=7.3 Hz), 7.45 (2H, t, J=7.6 Hz), 4.84 (1H, d, J=49.28 Hz), 4.25-3.91 (1H, m), 3.37-3.22 (2H, m), 3.10-2.95 (1H, m), 2.60-2.39 (2H, m), 2.32-2.02 (3H, m), 1.79 (1H, d, J=12.3 Hz), 1.11 (3H, t, J=7.2 Hz).

Workup

  1. customA 50 L autoclave was purged with nitrogen
  2. waitleft
  3. temperaturecooled to 25° C
  4. custompurge the contents of autoclave
  5. customwere transferred into a 60 L reactor with methanol (2.0 L)
  6. additionDeloxan THPII (2.4 kg, 40 mass %) was added
  7. filtrationThe suspension was filtered over Arbocel (0.7 kg)
  8. washthe filter cake was washed with methanol (5.0 L), and solvent
  9. customevaporated at 20 mbar and 45° C

Sources & evidence

ORD record
ord-8a3a1f140b39425da7573950b9f4d5f5
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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