Ammonium Chloride → tert-Butyl[6-chloro-3-(trifluoroacetyl)pyridin-2-yl]carbamate

HRID 1182992Notes

Reaction equation

HRID 1182992 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[F:21][C:22]([F:32])([F:31])[C:23](N1CCOCC1)=[O:24].[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[C:5]([C:23](=[O:24])[C:22]([F:32])([F:31])[F:21])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 5446364-(Trifluoroacetyl)morpholineHCID 11253185tert-butyl N-(6-chloropyridin-2-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 57911758tert-Butyl[6-chloro-3-(trifluoroacetyl)pyridin-2-yl]carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-50 °C

Procedure

8 g (35 mmol) of tert-butyl (6-chloropyridin-2-yl)carbamate (Example 1A) were initially charged in 100 ml of THF and cooled to −50° C. 55 ml (87 mmol) of butyllithium (1.6 N) were added dropwise. After the dropwise addition had ended, the reaction was warmed gradually to −10° C. and stirred at 0° C. for 2 h. Subsequently, the mixture was cooled again to −40° C., and 12.8 g (70 mmol) of 4-(trifluoroacetyl)morpholine (Example 6A), dissolved in 4 ml of THF, were added. The reaction solution was stirred at −40° C. for 1 h, then poured at −40° C. onto 1 l of ethyl acetate and 350 ml of ammonium chloride solution, and extracted. The organic phase was removed, dried over magnesium sulphate and concentrated on a rotary evaporator. The reaction mixture was chromatographed on silica gel (eluent: cyclohexane/ethyl acetate 10:1). 9 g (79% of theory) of the product were obtained as an oil.

Workup

  1. additionAfter the dropwise addition
  2. temperaturethe reaction was warmed gradually to −10° C.
  3. temperatureSubsequently, the mixture was cooled again to −40° C.
  4. additionwere added
  5. stirringThe reaction solution was stirred at −40° C. for 1 h
  6. extractionextracted
  7. customThe organic phase was removed
  8. dry with materialdried over magnesium sulphate
  9. concentrationconcentrated on a rotary evaporator
  10. customThe reaction mixture was chromatographed on silica gel (eluent: cyclohexane/ethyl acetate 10:1)
  11. custom9 g (79% of theory) of the product were obtained as an oil

Sources & evidence

ORD record
ord-372ec988044c4b2aa6b4454d9541f5a0
Source dataset
uspto-grants-2014_03
Patent number
US08664246B2

Reaction notes

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