Methane → HCID 59022871, compound

HRID 1888206Notes

Reaction equation

HRID 1888206 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:10])=[C:6]([CH:9]=1)[C:7]#[N:8].[Li+].CC([N-]C(C)C)C.CN(OC)[C:21]([CH:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1)=[O:22].[Cl-].[NH4+].C>C1COCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:9]=[C:6]([C:7]#[N:8])[C:5]([F:10])=[C:4]([C:21]([CH:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]2)=[O:22])[CH:3]=1

Participants

8

Reactant 5

HCID 297MethaneHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 27249005-Bromo-2-fluorobenzonitrileHCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

Product 1

HCID 59022871HCID 59022871, compoundYield 111.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 5-bromo-2-fluorobenzonitrile (7.34 g, 36.7 mmols) in dry THF (90 mL) was cooled to −78° C. under a nitrogen atmosphere. A 2M solution of LDA in THF (21.48 mL, 43.0 mmols) was added during 15 mins and the mixture was stirred at −78° C. for 2 h giving a deep blue solution. 1,1-dimethylethyl 4{[methyl(methyloxy)amino]carbonyl}-1-piperidinecarboxylate (12.5 g, 45.9 mmols) in dry THF (45 mL) was added and the reaction mixture was allowed to warm to room temperature and stirred for 16 hrs (overnight). Saturated aqueous ammonium chloride (200 mL) was added followed by ethyl acetate (200 mL). The mixture was treated with charcoal to decolorize, filtered and the organic phase separated. The organic layer was washed with saturated aqueous ammonium chloride and dried over MgSO4. Evaporation of the solvent afforded a green solid (16.8 g). The solid was purified by flash chromatography (Dry loaded onto silica, gradient elution with pentane/ethyl acetate 9:1 v/v to 3:2 v/v) to give the title compound (1.35 g) as a green gum (9%).

Workup

  1. customgiving a deep blue solution
  2. temperatureto warm to room temperature
  3. stirringstirred for 16 hrs (overnight)
  4. filtrationfiltered
  5. customthe organic phase separated
  6. washThe organic layer was washed with saturated aqueous ammonium chloride
  7. dry with materialdried over MgSO4
  8. customEvaporation of the solvent

Sources & evidence

ORD record
ord-ea8ab5c4ac7a47a0a500f7e25cbbaae0
Source dataset
uspto-grants-2013_08
Patent number
US08501780B2

Reaction notes

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