Tert-Butanesulfinamide → N-(5'-bromo-4-methoxyspiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide

HRID 473008ノート

反応式

HRID 473008 の反応式
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:16][CH2:15][CH:14]([O:17][CH3:18])[CH2:13][CH2:12]3)[C:8]2=O)=[CH:4][CH:3]=1.[CH3:19][C:20]([S:23]([NH2:25])=[O:24])([CH3:22])[CH3:21]>C1COCC1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5](=[CH:4][CH:3]=1)[CH2:6][C:7]1([CH2:16][CH2:15][CH:14]([O:17][CH3:18])[CH2:13][CH2:12]1)[C:8]2=[N:25][S:23]([C:20]([CH3:22])([CH3:21])[CH3:19])=[O:24]

参加物

4

反応物 2

HCID 3382465Tert-Butanesulfinamide3 回HCID 581972636'-bromo-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-one

生成物 1

HCID 67043683N-(5'-bromo-4-methoxyspiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide収率 78.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 6′-bromo-4-methoxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (3) (923 mg, 2.99 mmol) and 2-methylpropane-2-sulfinamide (1.450 g, 11.96 mmol, 4 eq.) in anhydrous THF (75 mL) was added Ti(OEt)4 (5.46 g, 4.96 mL, 23.92 mmol, 8.0 eq). The resulting mixture was heated to reflux overnight. LC-MS showed ca. 45% conversion. After another 8 h, no further improvement. To the refluxing mixture was added 2-methylpropane-2-sulfinamide (0.725 g, 5.98 mmol, 2 eq.) and Ti(OEt)4 (2.73 g, 2.5 mL, 11.96 mmol, 4.0 eq) and followed by another equal portions of 2-methylpropane-2-sulfinamide and Ti(OEt)4 after 14 hours. The reaction mixture was refluxed for another 2 days, 93% conversion achieved at this point. The reaction was quenched with brine (3 mL) after cooled down to room temperature. The mixture was stirred for another 30 min before filtered through a short pad of Celite®. The filter cake was washed with EA, and the filtrate was concentrated to dryness. The residue was purified by silica gel chromatography. The fraction of desired product with 2-methylpropane-2-sulfinamide was dissolved in EA (100 mL) and washed with saturated aqueous NaHCO3 (45 mL), 1 M NaOH (40 mL) and brine successively. Solvent was removed under reduced pressure after dried over Na2SO4 and filtered to afford 0.968 g of the desired product 4 as a light yellow solid. MS ESI+ve m/z 412 (M+H)+.

後処理

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux overnight
  3. temperatureThe reaction mixture was refluxed for another 2 days
  4. customThe reaction was quenched with brine (3 mL)
  5. filtrationbefore filtered through a short pad of Celite®
  6. washThe filter cake was washed with EA
  7. concentrationthe filtrate was concentrated to dryness
  8. customThe residue was purified by silica gel chromatography
  9. dissolutionThe fraction of desired product with 2-methylpropane-2-sulfinamide was dissolved in EA (100 mL)
  10. washwashed with saturated aqueous NaHCO3 (45 mL), 1 M NaOH (40 mL) and brine successively
  11. customSolvent was removed under reduced pressure
  12. dry with materialafter dried over Na2SO4
  13. filtrationfiltered

出典と根拠

ORDレコード
ord-86add306b06c4354935d6a797859ad1c
出典データセット
uspto-grants-2014_01
特許番号
US08633212B2

反応ノート

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