Hydrochloric Acid → HCID 86664579, compound

HRID 1631391Notes

Reaction equation

HRID 1631391 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.C([Mg]Cl)(C)C.[O:14]=[C:15]1[N:19]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:18]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:17][CH2:16]1.Cl.[NH4+].[Cl-]>C1COCC1.CCCCCCC.CC(OC)(C)C>[C:23]([O:22][C:20]([NH:19][C@@H:18]([CH2:17][CH2:16][C:15]([C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1)=[O:14])[C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:21])([CH3:24])([CH3:26])[CH3:25]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 8202063-Bromo-5-fluoropyridineHCID 54611861-(1,1-Dimethylethyl) 2-ethyl (2S)-5-oxo-1,2-pyrrolidinedicarboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 86664579HCID 86664579, compoundYield 102.3%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent3×HCID 8900HeptaneSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-bromo-5-fluoropyridine (4.28 g, 24.3 mmol) in dry THF (25 mL) was cooled to −40 to −50° C. and 2M isopropylmagnesium chloride in THF (10.2 mL, 20.4 mmol) was added. The mixture was allowed to warm to 0° C. and was stirred for 30 minutes. The mixture was cooled to −20° C. and a solution of (S)-1-tert-butyl 2-ethyl 5-oxopyrrolidine-1,2-dicarboxylate (5.00 g, 19.4 mmol) in dry THF (15 mL) was added. The mixture was allowed to reach ambient temperature over 30 minutes and was stirred at ambient temperature for 30 minutes. The reaction was slowly quenched with 2M HCl (10 mL, 20.0 mmol) followed by 10% aqueous NH4Cl (10 mL). The mixture was stirred for 10 minutes and was transferred to a separatory funnel using MTBE rinses (10 mL). Heptane (15 mL) was added and the organic layer was removed. The organic layer was washed 10% aqueous NH4Cl (25 mL) and DI H2O (25 mL). The organic layer was concentrated to provide the crude product as a yellow oil (7.03 g, 102%).

Workup

  1. temperatureThe mixture was cooled to −20° C.
  2. waitto reach ambient temperature over 30 minutes
  3. stirringwas stirred at ambient temperature for 30 minutes
  4. stirringThe mixture was stirred for 10 minutes
  5. customwas transferred to a separatory funnel
  6. customthe organic layer was removed
  7. washThe organic layer was washed 10% aqueous NH4Cl (25 mL) and DI H2O (25 mL)
  8. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-952bcc7c2ff645a2be0f91a7f104cca0
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

Loading…