Ammonium Chloride → methyl(R)-2-tert-butoxycarbonylamino-6-(2,6-difluoropyridin-3-yl)-6-oxohexanoate

HRID 1436126Notes

Reaction equation

HRID 1436126 reaction equation
[Li+].CC([N-]C(C)C)C.[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[N:11]=1.[CH3:17][O:18][C:19]([C@H:21]1[CH2:26][CH2:25][CH2:24][C:23](=[O:27])[N:22]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[O:20].[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[C:31]([O:30][C:28]([NH:22][C@H:21]([CH2:26][CH2:25][CH2:24][C:23]([C:15]1[C:10]([F:9])=[N:11][C:12]([F:16])=[CH:13][CH:14]=1)=[O:27])[C:19]([O:18][CH3:17])=[O:20])=[O:29])([CH3:34])([CH3:33])[CH3:32]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 739342,6-DifluoropyridineHCID 2724682Lithium diisopropylamideHCID 107298291-(Tert-butyl) 2-methyl (R)-6-oxopiperidine-1,2-dicarboxylate

Product 1

HCID 69003687methyl(R)-2-tert-butoxycarbonylamino-6-(2,6-difluoropyridin-3-yl)-6-oxohexanoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

LDA (1.5 M solution in THF, 3.2 mL) was added to a solution of 2,6-difluoropyridine (492 mg) in THF (25 mL) at −78° C., and the reaction solution was stirred at −78° C. for 2.5 hours. A solution of (R)-6-oxopiperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (CAS No. 183890-36-0, 1.0 g) in THF (5 mL) was added to the reaction solution at −78° C. The reaction solution was stirred at −78° C. for one hour and at 0° C. for 2.5 hours. A saturated ammonium chloride solution and ethyl acetate were added to the reaction solution, and the mixture was heated to room temperature. Thereafter, the organic layer was separated, and the resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane:ethyl acetate=1:1->ethyl acetate) to obtain 148 mg of the title compound. The property value of the compound is as follows.

Workup

  1. stirringThe reaction solution was stirred at −78° C. for one hour and at 0° C. for 2.5 hours
  2. temperaturethe mixture was heated to room temperature
  3. customThereafter, the organic layer was separated
  4. dry with materialthe resulting organic layer was dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (elution solvent: heptane:ethyl acetate=1:1->ethyl acetate)

Sources & evidence

ORD record
ord-b4e7230f5a2041f7872a61e23fbfb245
Source dataset
uspto-grants-2009_11
Patent number
US07618960B2

Reaction notes

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