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

HRID 2088648Notes

Reaction equation

HRID 2088648 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[N:9]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[F:21][C:22]([F:32])([F:31])[C:23](N1CCOCC1)=[O:24].[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[C:13]([C:23](=[O:24])[C:22]([F:32])([F:31])[F:21])=[CH:12][CH:11]=[C:10]([Cl:14])[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

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 3A) 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 slowly warmed to −10° C. and stirred at 0° C. for 2 h. The mixture was then cooled again to −40° C., and 12.8 g (70 mmol) of 4-(trifluoroacetyl)morpholine (Example 10A), dissolved in 4 ml of THF, were added. The reaction solution was stirred at −40° C. for 1 h and then, at −40° C., poured into 1 l of ethyl acetate and 350 ml of ammonium chloride solution and extracted. The organic phase was separated off, dried over magnesium sulfate and concentrated on a rotary evaporator. The reaction mixture was chromatographed on silica gel (mobile phase cyclohexane/ethyl acetate 10:1). This gave 9 g (79% of theory) of the product as an oil.

Workup

  1. additionAfter the dropwise addition
  2. temperaturethe reaction was slowly warmed to −10° C.
  3. temperatureThe mixture was then 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 separated off
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated on a rotary evaporator
  10. customThe reaction mixture was chromatographed on silica gel (mobile phase cyclohexane/ethyl acetate 10:1)

Sources & evidence

ORD record
ord-2e8bba036e9c433c9fd40740064657ce
Source dataset
uspto-grants-2013_05
Patent number
US08436003B2

Reaction notes

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