4-Acetylmorpholine → tert-Butyl [6-chloro-3-acetylpyridin-2-yl]carbamate

HRID 2171535Notes

Reaction equation

HRID 2171535 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.[C:21](N1CCOCC1)(=[O:23])[CH3:22].[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:21](=[O:23])[CH3:22])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 155434-AcetylmorpholineHCID 25517Ammonium ChlorideHCID 11253185tert-butyl N-(6-chloropyridin-2-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 59313093tert-Butyl [6-chloro-3-acetylpyridin-2-yl]carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-50 °C

Procedure

0.65 g (2.9 mmol) of tert-butyl (6-chloropyridin-2-yl)carbamate (Example 105A) is introduced into 10 ml of THF and cooled to −50° C. 4.5 ml (7.2 mmol) of butyllithium (1.6 M) are added dropwise. After the dropwise addition is complete, the reaction is slowly warmed to −10° C. and kept at 0° C. for 2 h. It is then cooled to −40° C. again, and 740 mg (5.7 mmol) of N-acetylmorpholine dissolved in 4 ml of THF are added. The reaction solution is 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 is separated off, dried over magnesium sulphate and concentrated in a rotary evaporator. The reaction mixture is chromatographed on silica gel (mobile phase cyclohexane/ethyl acetate 2:1). 218 mg (28% of theory) of the product are obtained as an oil.

Workup

  1. additionAfter the dropwise addition
  2. temperaturethe reaction is slowly warmed to −10° C.
  3. temperatureIt is then cooled to −40° C. again
  4. additionare added
  5. extractionextracted
  6. customThe organic phase is separated off
  7. dry with materialdried over magnesium sulphate
  8. concentrationconcentrated in a rotary evaporator
  9. customThe reaction mixture is chromatographed on silica gel (mobile phase cyclohexane/ethyl acetate 2:1)
  10. custom218 mg (28% of theory) of the product are obtained as an oil

Sources & evidence

ORD record
ord-0ce0c2b21dd34b3b9f07fd4a04768a9a
Source dataset
uspto-grants-2015_06
Patent number
US09051323B2

Reaction notes

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