Ammonium Chloride → tert-Butyl (6-chloro-3-propanoylpyridin-2-yl)carbamate

HRID 2088660Notes

Reaction equation

HRID 2088660 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.[C:21](N1CCOCC1)(=[O:24])[CH2:22][CH3:23].[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[C:13]([C:21](=[O:24])[CH2:22][CH3:23])=[CH:12][CH:11]=[C:10]([Cl:14])[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2254471-(4-Morpholinyl)-1-propanoneHCID 11253185tert-butyl N-(6-chloropyridin-2-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 57911766tert-Butyl (6-chloro-3-propanoylpyridin-2-yl)carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-50 °C

Procedure

Under argon, 7.00 g (30.6 mmol) of tert-butyl(6-chloropyridin-2-yl)carbamate (Example 3A) were initially charged in 90 ml of THF and cooled to −50° C. 47.8 ml (76.5 mmol) of butyllithium (1.6 M in hexane) were added dropwise. After the dropwise addition had ended, the reaction was slowly warmed to 0° C. and kept at 0° C. for 1 h. The mixture was then cooled again to −40° C., and 9.85 g (61.2 mmol) of N-propionylmorpholine dissolved in 10 ml of THF were added. The reaction solution was stirred at −40° C. for another 1 h and then, at −40° C., poured into 1 l of ethyl acetate and 350 ml of ammonium chloride solution, and the organic phase was separated off and washed with water and saturated aqueous sodium bicarbonate solution. The organic phase was dried over magnesium sulfate and concentrated on a rotary evaporator. The crude product was chromatographed on silica gel (mobile phase cyclohexane/ethyl acetate 10:1 to 1:1). This gave 2800 mg (32% of theory) of the product.

Workup

  1. additionAfter the dropwise addition
  2. temperaturethe reaction was slowly warmed to 0° C.
  3. temperatureThe mixture was then cooled again to −40° C.
  4. additionwere added
  5. customthe organic phase was separated off
  6. washwashed with water and saturated aqueous sodium bicarbonate solution
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. concentrationconcentrated on a rotary evaporator
  9. customThe crude product was chromatographed on silica gel (mobile phase cyclohexane/ethyl acetate 10:1 to 1:1)

Sources & evidence

ORD record
ord-2111fd3b22db47348de7657ff1293d62
Source dataset
uspto-grants-2013_05
Patent number
US08436003B2

Reaction notes

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