Acetophenone → [4-(2-Hydroxy-2-phenyl-propyl)-pyridin-2-yl]-carbamic acid tert-butyl ester

HRID 1023428

反応式

HRID 1023428 の反応式
[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.CCCCCC.[C:27]1([C:33](=[O:35])[CH3:34])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=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:33]([OH:35])([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH3:34])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

9

反応物 5

HCID 7410AcetophenoneHCID 8058HexaneHCID 25517Ammonium ChlorideHCID 11063648tert-butyl N-(4-methylpyridin-2-yl)carbamateHCID 178418339Butyllithium

生成物 1

HCID 69083970[4-(2-Hydroxy-2-phenyl-propyl)-pyridin-2-yl]-carbamic acid tert-butyl ester収率 88.8%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

The solution of (4-methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (100 mg, 0.48 mmol) in dry THF (5 mL) is cooled down to −78° C. The 1.6 M n-BuLi in hexane solution (1.5 mL, 2.4 mmol) is added dropwise at −78° C. Then the cooling bath is removed and the mixture is stirred at room temperature for 15 min. The reaction mixture is cooled down to −78° C. again and 1-phenyl-ethanone (0.28 mL, 2.4 mmol) is added. The mixture is stirred for another 30 min at −78° C. and saturated NH4Cl aquaous solution (25 mL) is added. The reaction mixture is then warmed up to room temperature and EtOAc (50 mL) is added along with water (30 mL). The resulting mixture is stirred for 10 min and the aqueous layer is separated and 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%) afforded 140 mg of desired product.

後処理

  1. customThen the cooling bath is removed
  2. temperatureThe reaction mixture is cooled down to −78° C. again
  3. stirringThe mixture is stirred for another 30 min at −78° C.
  4. temperatureThe reaction mixture is then warmed up to room temperature
  5. stirringThe resulting mixture is stirred for 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

出典と根拠

ORDレコード
ord-1a331fce76c44850a1639a3da1d979ec
出典データセット
uspto-grants-2014_05
特許番号
US08722709B2

関連ノート

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