Water → HCID 67464294, compound

HRID 553936Notes

Reaction equation

HRID 553936 reaction equation
C(NC(C)C)(C)C.[F:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[N:10]=1.[CH3:16][CH2:17][O:18][C:19]([C@H:21]1[CH2:25][CH2:24][C:23](=[O:26])[N:22]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[O:20].O>O1CCCC1.C([Li])CCC>[C:30]([O:29][C:27]([NH:22][C@H:21]([CH2:25][CH2:24][C:23]([C:14]1[C:9]([F:8])=[N:10][C:11]([F:15])=[CH:12][CH:13]=1)=[O:26])[C:19]([O:18][CH2:17][CH3:16])=[O:20])=[O:28])([CH3:31])([CH3:33])[CH3:32]

Participants

7

Reactant 4

HCID 962WaterHCID 7912DiisopropylamineHCID 739342,6-DifluoropyridineHCID 8208851-Boc-D-Pyroglutamic acid ethyl ester

Product 1

HCID 67464294HCID 67464294, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 178418339ButyllithiumSolvent

Procedure

To a solution of diisopropylamine (0.653 mL) in tetrahydrofuran (30 mL), n-butyl lithium (1.57 M solution in hexane, 2.97 mL) was added at −78° C. over five minutes, and the reaction solution was stirred at the same temperature for 20 minutes. 2,6-Difluoropyridine (0.388 mL) was added dropwise to the solution at −78° C., and the reaction solution was stirred at −78° C. for three hours. A solution of (R)-5-oxopyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (1.0 g) in tetrahydrofuran (5.0 mL) was added dropwise to this solution at −78° C., and the reaction solution was stirred at 0° C. for one hour. Water was added to the solution in small portions at 0° C., followed by extraction with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (heptane-ethyl acetate system) to obtain 1.2 g of the title compound as a pale yellow oil. The property values of the compound are as follows.

Workup

  1. stirringthe reaction solution was stirred at −78° C. for three hours
  2. stirringthe reaction solution was stirred at 0° C. for one hour
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-2b7938f9117946608e81ea5e8615205b
Source dataset
uspto-grants-2011_11
Patent number
US08048878B2

Reaction notes

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