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

HRID 444833

반응식

HRID 444833 반응식
[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:27])([F:26])[C:23](O)=[O:24].ClC1C=C(Cl)C=CC=1C1NC(=O)C2N(N=C(CN3CCOCC3)C=2)C=1.[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:27])([F:26])[F:21])=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 11253185tert-butyl N-(6-chloropyridin-2-yl)carbamateHCID 670601896-(2,4-Dichlorophenyl)-2-(morpholin-4-ylmethyl)pyrazolo[1,5-a]pyrazin-4(5H)-one trifluoroacetateHCID 178418339Butyllithium

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
-50 °C

실험 절차

8 g (35 mmol) of tert-butyl (6-chloropyridin-2-yl)carbamate (Example 24A) were initially charged in 100 ml of THF and cooled to −50° C. 55 ml (87 mmol) of butyllithium (1.6N) 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 21A), dissolved in 4 ml of THF, were added. The reaction solution was stirred at −40° C. for 1 h, and, 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.

후처리

  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)

출처 및 근거

ORD 기록
ord-dba4338d220d456e8d517bb035f70260
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08476267B2

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