Hydrochloric Acid → HCID 20741392, compound

HRID 1883966Notes

Reaction equation

HRID 1883966 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.CN(OC)[C:15]([C@@H:17]1[CH2:21][C:20](=[O:22])[N:19]([C@@H:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH3:24])[CH2:18]1)=[O:16].Cl>O1CCCC1>[C:25]1([C@H:23]([N:19]2[CH2:18][C@H:17]([C:15]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=3)=[O:16])[CH2:21][C:20]2=[O:22])[CH3:24])[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 79732-BromopyridineHCID 20741434HCID 20741434, compoundHCID 178418339Butyllithium

Product 1

HCID 20741392HCID 20741392, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In an atmosphere of nitrogen and at −78° C., n-butyl lithium (1.5 mol/l tetrahydrofuran solution; 13.2 ml, 19.9 mmol) was added dropwise to a tetrahydrofuran solution (40 ml) of 2-bromopyridine (1.94 ml, 19.9 mmol), and then the mixture was stirred for 10 minutes. At −78° C., to this was further added dropwise a tetrahydrofuran solution (20 ml) of N-methyl-N-methoxy-1-(1-(R)-phenylethyl]-5-oxopyrrolidine-3-(R)-carboxamide (3.66 g, 13.2 mmol), and the mixture was stirred for 30 minutes. The reaction solution was mixed with 1 mol/l hydrochloric acid (200 ml), warmed up to room temperature and then extracted with diethyl ether (200 ml×2). The resulting organic layer was washed with saturated brine (100 ml) and dried over anhydrous magnesium sulfate. The solvent was evaporated under a reduced pressure and the residue was applied to a silica gel column chromatography (silica gel 100 g). By eluting with a n-hexane:ethyl acetate system of from (3:1) to (1:1), 1.97 g (52%) of the title compound was obtained as a light yellow oil. 1H-NMR (400 MHz, CDCl3) δ: 1.54 (3H, d, J=7.08 Hz), 2.80-2.83 (2H, m), 3.35 (1H, t, J=9.37 Hz), 3.61 (1H, dd, J=6.35, 9.37 Hz), 4.49-4.54 (1H, m), 5.54 (1H, q, J=7.08 Hz), 7.25-7.38 (5H, m), 7.47-7.50 (1H, m), 7.86 (1H, dt, J=1.71, 7.81 Hz), 8.08 (1H, d, J=7.81 Hz), 8.64-8.65 (1H, m).

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. extractionextracted with diethyl ether (200 ml×2)
  3. washThe resulting organic layer was washed with saturated brine (100 ml)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under a reduced pressure
  6. washBy eluting with a n-hexane

Sources & evidence

ORD record
ord-b25f2cc3f169483d81d2285cd6fe5aa5
Source dataset
uspto-grants-2004_07
Patent number
US06762181B1

Reaction notes

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