Sodium Carbonate → Tert-butyl 1-(3-bromo-5-fluoropyridin-4-yl)piperidine-4-carboxylate

HRID 524886Notes

Reaction equation

HRID 524886 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Cl.[Br:8][C:9]1[CH:10]=[N:11][CH:12]=[C:13]([F:16])[C:14]=1Cl.[NH:17]1[CH2:22][CH2:21][CH:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1>C1(O)CCCCC1>[Br:8][C:9]1[CH:10]=[N:11][CH:12]=[C:13]([F:16])[C:14]=1[N:17]1[CH2:22][CH2:21][CH:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 1512676Tert-butyl Piperidine-4-carboxylateHCID 867209403-Bromo-4-chloro-5-fluoropyridine hydrochloride

Product 1

HCID 86720943Tert-butyl 1-(3-bromo-5-fluoropyridin-4-yl)piperidine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 7966CyclohexanolSolvent

Conditions

Temperature
40 °C

Procedure

A 3 L flange flask equipped with a thermometer, condensor, nitrogen line and overhead stirrer was heated at 40° C. (external) then charged with cyclohexanol (750 mL), disodium carbonate (129.8 g, 1.225 mol), 3-bromo-4-chloro-5-fluoro-pyridine (Hydrochloric Acid 18) (137.5 g, 556.8 mmol) and tert-butyl piperidine-4-carboxylate (123.8 g, 668.2 mmol) rinsed in with cyclohexanol (350 mL). Mixture was heated to 120° C. internal temperature overnight (18 h). Reaction mixture was removed from hotplate and allowed to cool to room temperature. Water (687.5 mL) and EtOAc (687.5 mL) were added, stirred for 10 mins then transferred to separating funnel Additional EtOAc (1.238 L) was added, mixed and aqueous phase was removed. Organic phase was further washed with water (687 mL), aqueous phase removed, organic layer collected. Aqueous phases were combined and back extracted with EtOAc (687.5 mL), aqueous layer removed and organic phase combined with other organics. Organics concentrated in vacuo (water bath temp=60° C., vacuum down to 2 mBar) leaving a viscous brown oil.

Workup

  1. customA 3 L flange flask equipped with a thermometer, condensor, nitrogen line and overhead stirrer
  2. washrinsed in with cyclohexanol (350 mL)
  3. temperatureMixture was heated to 120° C. internal temperature overnight (18 h)
  4. customReaction mixture
  5. customwas removed from hotplate
  6. temperatureto cool to room temperature
  7. additionWater (687.5 mL) and EtOAc (687.5 mL) were added
  8. customto separating funnel Additional EtOAc (1.238 L)
  9. additionwas added
  10. additionmixed
  11. customaqueous phase was removed
  12. washOrganic phase was further washed with water (687 mL), aqueous phase
  13. customremoved
  14. customorganic layer collected
  15. extractionback extracted with EtOAc (687.5 mL), aqueous layer
  16. customremoved
  17. concentrationOrganics concentrated in vacuo (water bath temp=60° C., vacuum down to 2 mBar)
  18. customleaving a viscous brown oil

Sources & evidence

ORD record
ord-0d64f54ca0304f9da019d11cc9fdb5a5
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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