N-methyl-2-pyrrolidone → 2-Tert-butoxy-2-(1-(4-chlorophenyl)-4-cyano-3-methylnaphthalen-2-yl)acetic acid

HRID 514149ノート

反応式

HRID 514149 の反応式
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[C:4]([CH:19]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:20]([O:22]C)=[O:21])[C:3]=1[CH3:29].[C:30]([Cu])#[N:31].CN1C(=O)CCC1>CCO>[C:25]([O:24][CH:19]([C:4]1[C:3]([CH3:29])=[C:2]([C:30]#[N:31])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]=1[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)[C:20]([OH:22])=[O:21])([CH3:26])([CH3:28])[CH3:27]

参加物

5

反応物 3

HCID 13387N-methyl-2-pyrrolidoneHCID 67126267Methyl 2-(4-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetateHCID 178418546HCID 178418546、化合物

生成物 1

HCID 671263162-Tert-butoxy-2-(1-(4-chlorophenyl)-4-cyano-3-methylnaphthalen-2-yl)acetic acid収率 57.7%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
200 °C

実験手順

A suspension of methyl 2-(4-bromo-1-(4-chlorophenyl)-3-methylnaphthalen-2-yl)-2-tert-butoxyacetate (10.5 mg, 22.1 μmol), CuCN (9.8 mg, 0.11 mmol), and NMP (500 μL) was heated to 200° C. in a microwave. The reaction was cooled to 23° C., treated with EtOH (2.5 mL), filtered through a 0.45 micron filter, and directly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA). The product-containing fractions were combined and treated with LiOH monohydrate until the pH was distinctly basic. The mixture was concentrated with warming to remove most of the water and all of the CH3CN. The solution was treated with EtOH (absolute, 500 μL) and THF (1.0 mL). The suspension was stirred at 23° C. for 1 h. It was filtered through a 0.45 micron filter, and directly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA). The product-containing fractions were combined and lyophilized, giving the title compound (parent form) (5.2 mg, 55% over 2 steps).

後処理

  1. temperatureThe reaction was cooled to 23° C.
  2. filtrationfiltered through a 0.45 micron
  3. filtrationfilter
  4. customdirectly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA)
  5. additiontreated with LiOH monohydrate until the pH
  6. concentrationThe mixture was concentrated
  7. temperaturewith warming
  8. customto remove most of the water
  9. additionThe solution was treated with EtOH (absolute, 500 μL) and THF (1.0 mL)
  10. filtrationIt was filtered through a 0.45 micron
  11. filtrationfilter
  12. customdirectly purified by reverse phase HPLC (Gemini, 5 to 100% ACN/H2O+0.1% TFA)

出典と根拠

ORDレコード
ord-bde06fe26a96414bb8fbc1ed9ed9f99c
出典データセット
uspto-grants-2015_08
特許番号
US09102614B2

反応ノート

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