Butyl vinyl ether → tert-butyl 5'-acetyl-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate

HRID 1508290ノート

反応式

HRID 1508290 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7]1([CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]1)[O:6][CH2:5]2.[CH:21]([O:23]CCCC)=[CH2:22].C([O-])(O)=O.[Na+]>C(O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:21]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7]1([CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]1)[O:6][CH2:5]2)(=[O:23])[CH3:22]

参加物

7

反応物 3

HCID 8108Butyl vinyl etherHCID 516892Sodium BicarbonateHCID 66555337tert-Butyl 5'-bromo-3'h-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate2 回

生成物 1

HCID 70663143tert-butyl 5'-acetyl-3'H-spiro[azetidine-3,1'-isobenzofuran]-1-carboxylate収率 94.2%

試薬・触媒・溶媒 3

HCID 812191,3-Bis(diphenylphosphino)propane触媒HCID 167845palladium(II) acetate触媒HCID 702Ethanol溶媒

反応条件

温度
96 °C

実験手順

In 100 mL autoclave vessel a solution of tert-butyl 5′-bromo-3′H-spiro[azetidine-3,1′-isobenzofuran]-1-carboxylate (Intermediate 1, 10 g, 29.4 mmol) in ethanol (35 mL) was degassed with nitrogen gas for 30 minutes. To the resulting reaction mixture was added TEA (7.37 mL, 52.9 mmol), butyl vinyl ether (7.60 mL, 58.8 mmol), dppp (0.727 g, 1.8 mmol) followed by addition of Pd(OAc)2 (0.198 g, 0.9 mmol) at room temperature. Reaction mixture was heated at 96° C. for 16 hours in autoclave. After complete consumption of starting material, reaction mixture was quenched with addition of 1N HCl (10 mL) to adjust pH 2-3 then reaction mixture was stirred for 2 hours. The pH of reaction mixture was adjusted to 7 by addition of saturated NaHCO3 solution and extracted with ethyl acetate (3×100 mL). Combined organic layers were washed with brine (250 mL), dried over sodium sulfate and concentrated under reduced pressure to get crude compound as dark brown sticky oil 12 g as crude material. The crude was purified by column chromatography on silica gel using 230-400 silica mesh. Desired compound was eluted in 30% ethyl acetate in n-hexane to give (8.4 g) compound as off white sticky semi-solid. 1H NMR (400 MHz, CDCl3) δ: 1.47 (s, 9H), 2.61 (s, 3H), 4.13 (d, J=9.64 Hz, 2H), 4.32 (d, J=9.52 Hz, 2H), 5.14 (s, 2H), 7.54 (d, J=7.96 Hz, 1H), 7.80 (s, 1H), 7.97 (d, J=7.92 Hz, 1H); VETERINARY (m/z): 304.0 (M+H).

後処理

  1. customTo the resulting reaction mixture
  2. customReaction mixture
  3. customAfter complete consumption of starting material, reaction mixture
  4. customwas quenched with addition of 1N HCl (10 mL)
  5. customreaction mixture
  6. customThe pH of reaction mixture
  7. extractionextracted with ethyl acetate (3×100 mL)
  8. washCombined organic layers were washed with brine (250 mL)
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customto get crude compound as dark brown sticky oil 12 g as crude material
  12. customThe crude was purified by column chromatography on silica gel using 230-400 silica mesh
  13. washDesired compound was eluted in 30% ethyl acetate in n-hexane

出典と根拠

ORDレコード
ord-bd976e40335c4781b728cec7dc952c54
出典データセット
uspto-grants-2015_12
特許番号
US09221835B2

反応ノート

読み込み中…