Ammonium Chloride → [4-(2-Hydroxy-2-phenyl-2-o-tolyl-ethyl)-pyridin-2-yl]-carbamic acid tert-butyl ester

HRID 1023436

반응식

HRID 1023436 반응식
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[C:21]1([C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])=[O:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[NH4+].[Cl-]>C1COCC1.O.CCOC(C)=O>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[C:12]([CH2:14][C:27]([OH:28])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 25517Ammonium ChlorideHCID 672302-MethylbenzophenoneHCID 11063648tert-butyl N-(4-methylpyridin-2-yl)carbamateHCID 178418339Butyllithium

생성물 1

HCID 69675871[4-(2-Hydroxy-2-phenyl-2-o-tolyl-ethyl)-pyridin-2-yl]-carbamic acid tert-butyl ester수율 63.7%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
-78 °C

실험 절차

(4-Methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (300 mg, 1.4 mmol) is dissolved in dry THF (15 mL) and it is cooled down to −78° C. After 1.6 M n-BuLi (4.5 mL, 7.2 mmol) is added at −78° C., the cooling bath is removed and the mixture is stirred at room temperature for 15 min. Then the reaction mixture is cooled down to −78° C. again and phenyl-o-tolyl-methanone (1.3 mL, 7.2 mmol) is added. After the mixture is stirred for 30 min at −78° C., saturated NH4Cl aqueous solution (15 mL) is added and the reaction is warmed up to room temperature. EtOAc (60 mL) is added along with water (50 mL). The mixture is stirred for another 10 min and the aqueous layer is separated, extracted with EtOAc (2×35 ml). The organic layers are combined and concentrated to give the crude product. Purification by silica flash column chromatography using MeOH in DCM (gradient from 0% to 10%) affords 361 mg of the desired product.

후처리

  1. customthe cooling bath is removed
  2. temperatureThen the reaction mixture is cooled down to −78° C. again
  3. stirringAfter the mixture is stirred for 30 min at −78° C.
  4. temperaturethe reaction is warmed up to room temperature
  5. stirringThe mixture is stirred for another 10 min
  6. customthe aqueous layer is separated
  7. extractionextracted with EtOAc (2×35 ml)
  8. concentrationconcentrated
  9. customto give the crude product
  10. customPurification by silica flash column chromatography

출처 및 근거

ORD 기록
ord-9f4e2f29d02541fdb765fd40f9aa9751
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08722709B2

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