Ethyl 6-chloronicotinate → Ethyl 6-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)ethynyl]nicotinoate

HRID 128920

反応式

HRID 128920 の反応式
[CH3:1][C:2]1([CH3:16])[C:11]2[C:6](=[CH:7][C:8]([C:12]#[CH:13])=[CH:9][CH:10]=2)[C:5]([CH3:15])([CH3:14])[CH2:4][CH2:3]1.C([Li])CCC.Cl[C:23]1[CH:33]=[CH:32][C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:25][N:24]=1>CCCCCC.C1COCC1>[CH3:1][C:2]1([CH3:16])[CH2:3][CH2:4][C:5]([CH3:15])([CH3:14])[C:6]2[CH:7]=[C:8]([C:12]#[C:13][C:23]3[CH:33]=[CH:32][C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:25][N:24]=3)[CH:9]=[CH:10][C:11]1=2

参加物

6

反応物 3

HCID 2799611Ethyl 6-chloronicotinateHCID 147265491,1,4,4-Tetramethyl-6-ethynyl-1,2,3,4-tetrahydronaphthaleneHCID 178418339Butyllithium

生成物 1

HCID 15228883Ethyl 6-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)ethynyl]nicotinoate

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒4 回HCID 8058Hexane溶媒

反応条件

温度
0 °C

実験手順

The reaction vessels used in this procedure were flame dried under vacuum and all operations were carried out in an oxygen-free argon or nitrogen atmosphere. To a solution of 417.6 mg (1.9667 mmol) of 1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-6-ethynylnapthalene in 3 ml of dry tetrahydrofuron (THF) at 0° C. was added dropwise 1.3 ml of 1.6M (2.32 mmol) n-butyllithium in hexane. This mixture was stirred at 0° C. for 10 minutes and at room temperature for 15 minutes, cooled again to 0° C. and then treated by double-ended needle with a solution of 290 mg (2.1279 mmol) of fused zinc chloride in 4 ml dry THF. The mixture was stirred at 0° C. for 45 minutes and at room temperature for 15 minutes. A solution of 361.1 mg (1.9455 mmol) of ethyl 6-chloronicotinoate in 4 ml dry THF was transferred by double ended needle into a suspension of 420 mg (0.3635 mmol) of tetrakistriphenylphosphine palladium in 4 ml dry THF, the resultant mixture stirred at room temperature for 15 minutes and then treated by double ended needle with the solution of alkynyl zinc prepared above. The reaction mixture was stirred at room temperature for 70 hours and then quenched with ice and 30 ml of 3N HCl. The resultant mixture was extracted with 3×50 ml of ether, the ether extracts combined and washed successively with saturated NaHCO3 and saturated NaCl solutions and then dried (MgSO4). The ether solution was filtered and concentrated in-vacuo. The resultant crude product was purified by flash chromatography (silica, 10% ethyl acetate in hexanes) followed by recrystallization from a mixture of ethylacetate in hexane to give the title compound as a pale cream solid.

後処理

  1. customThe reaction vessels
  2. temperaturewere flame
  3. customdried under vacuum
  4. temperaturecooled again to 0° C.
  5. stirringThe mixture was stirred at 0° C. for 45 minutes and at room temperature for 15 minutes
  6. customprepared above
  7. stirringThe reaction mixture was stirred at room temperature for 70 hours
  8. customquenched with ice and 30 ml of 3N HCl
  9. extractionThe resultant mixture was extracted with 3×50 ml of ether
  10. washwashed successively with saturated NaHCO3 and saturated NaCl solutions
  11. dry with materialdried (MgSO4)
  12. filtrationThe ether solution was filtered
  13. concentrationconcentrated in-vacuo
  14. customThe resultant crude product was purified by flash chromatography (silica, 10% ethyl acetate in hexanes)
  15. customfollowed by recrystallization from a mixture of ethylacetate in hexane

出典と根拠

ORDレコード
ord-74299b7792cf4f2aaafd18295392240b
出典データセット
uspto-grants-1995_11
特許番号
US05466690

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