Methanesulfonic Acid → 6-(tert-Butyl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 2069794

反応式

HRID 2069794 の反応式
[C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[CH2:9][CH2:8]2)([CH3:4])([CH3:3])[CH3:2].CS(O)(=O)=O.[N-:20]=[N+]=[N-].[Na+]>ClCCl>[C:1]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[C:10](=[O:14])[NH:20][CH2:9][CH2:8]2)([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 6395Methanesulfonic AcidHCID 33557Sodium AzideHCID 110305765-Tert-butyl-2,3-dihydroinden-1-one2 回

生成物 1

HCID 598366606-(tert-Butyl)-3,4-dihydroisoquinolin-1(2H)-one収率 42.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To 5-tert-Butyl-indan-1-one (15.7 g, 83.4 mmol) in dichloromethane (150 mL) was added methanesulfonic acid (100 mL) and the resulting mixture was cooled to 0° C. Then sodium azide (10.83 g, 2 eq) was added carefully portion-wise over 15 minutes. The resulting mixture was stirred at 0° C. for about 2.5 hours. TLC analysis confirmed that all of the 5-tert-Butyl-indan-1-one had been consumed. With stirring at 0° C. was added very carefully a solution of aqueous sodium hydroxide (20%) until pH=14. Then added dichloromethane (1000 mL) and water (500 mL) which results in a large emulsion. The layers were separated and the aqueous layer was further extracted with dicholormethane (2×200 mL). Finally the combined dichloromethane layers were washed with brine (9×200 mL), dried over magnesium sulfate and filtered through a bed of celite. After concentrating and pumping to dryness there was 13.5 g of crude product as a tan solid. Purification on a 400 g Analogix Column eluting with a gradient of 10% to 60% ethyl acetate in hexane provided the correct isomer as a white powder (7.22 g) ((M+H)+=204) and the undesired isomer (1.555 g) as a white powder.

後処理

  1. customhad been consumed
  2. stirringWith stirring at 0° C.
  3. additionwas added very carefully a solution of aqueous sodium hydroxide (20%) until pH=14
  4. customThen added dichloromethane (1000 mL) and water (500 mL) which results in a large emulsion
  5. customThe layers were separated
  6. extractionthe aqueous layer was further extracted with dicholormethane (2×200 mL)
  7. washFinally the combined dichloromethane layers were washed with brine (9×200 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered through a bed of celite
  10. concentrationAfter concentrating
  11. customPurification on a 400 g Analogix Column
  12. washeluting with a gradient of 10% to 60% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-a7255a51e07a4d37b6fd070e795044ac
出典データセット
uspto-grants-2012_10
特許番号
US08299077B2

関連ノート

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