1-Acetylpiperazine → 4-(4-Acetylpiperazin-1-yl)-2-fluorobenzaldehyde

HRID 1505600ノート

反応式

HRID 1505600 の反応式
CC(C)([O-])C.[Na+].[N:7]1([C:13](=[O:15])[CH3:14])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.Br[C:17]1[CH:22]=[CH:21][C:20]([CH:23](OC)[O:24]C)=[C:19]([F:28])[CH:18]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>[C:13]([N:7]1[CH2:12][CH2:11][N:10]([C:17]2[CH:22]=[CH:21][C:20]([CH:23]=[O:24])=[C:19]([F:28])[CH:18]=2)[CH2:9][CH2:8]1)(=[O:15])[CH3:14]

参加物

7

反応物 3

HCID 837951-AcetylpiperazineHCID 184268214-Bromo-1-(dimethoxymethyl)-2-fluorobenzeneHCID 23676156Sodium t-butoxide

生成物 1

HCID 866906364-(4-Acetylpiperazin-1-yl)-2-fluorobenzaldehyde収率 60%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

Palladium(II) acetate (111 mg, 0.49 mmol), 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl (469 mg, 0.98 mmol) and sodium tert-butoxide (4.88 g, 49.2 mmol) were combined and the flask was purged with nitrogen. A solution of 1-piperazin-1-ylethanone (4.1 g, 32 mmol) and 4-bromo-1-(dimethoxymethyl)-2-fluoro-benzene (6.13 g, 24.6 mmol) in 1,4-dioxane (82 mL) was then added and the reaction was stirred at 100° C. for 16 hours. The reaction was then filtered through diatomaceous earth and concentrated. The resulting residue was dissolved in 50 mL of THF and 50 mL of 1 N aqueous HCl was added and the reaction was stirred at ambient temperature for 16 hours. The reaction was then neutralized with saturated aqueous Na2CO3 and extracted with dichloromethane (×3), dried with MgSO4, concentrated and purified by silica gel column chromatography (0-10% methanol in dichloromethane) to give 4-(4-acetylpiperazin-1-yl)-2-fluoro-benzaldehyde (3.68 g, 60% yield). LCMS (m/z) ES+ 251 [M+1]+.

後処理

  1. customthe flask was purged with nitrogen
  2. filtrationThe reaction was then filtered through diatomaceous earth
  3. concentrationconcentrated
  4. dissolutionThe resulting residue was dissolved in 50 mL of THF
  5. addition50 mL of 1 N aqueous HCl was added
  6. stirringthe reaction was stirred at ambient temperature for 16 hours
  7. extractionextracted with dichloromethane (×3)
  8. dry with materialdried with MgSO4
  9. concentrationconcentrated
  10. custompurified by silica gel column chromatography (0-10% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-ea071627445846a6b0062822ff2b26f4
出典データセット
uspto-grants-2015_12
特許番号
US09216988B2

反応ノート

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