Benzene → (NE,R)-N-[(2S)-2-(2,3-difluorophenyl)hex-5-enylidene]-2-methylpropane-2-sulfinamide

HRID 403339Notes

Reaction equation

HRID 403339 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:9]([CH2:12][CH2:13][CH:14]=[CH2:15])[CH:10]=O.C1C=CC=CC=1.[CH3:22][C:23]([S@:26]([NH2:28])=[O:27])([CH3:25])[CH3:24]>O1CCCC1.[Cl-].[Na+].O.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:9]([CH2:12][CH2:13][CH:14]=[CH2:15])/[CH:10]=[N:28]/[S@@:26]([C:23]([CH3:25])([CH3:24])[CH3:22])=[O:27]

Participants

7

Reactant 3

HCID 241BenzeneHCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 86681332HCID 86681332, compound

Product 1

HCID 89158770(NE,R)-N-[(2S)-2-(2,3-difluorophenyl)hex-5-enylidene]-2-methylpropane-2-sulfinamideYield 73.1%

Reagents, catalysts & solvents 3

HCID 76524Titanium tetraethoxideCatalystHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

In a 500 mL round-bottomed flask was dissolved (S)-2-(2,3-difluorophenyl)hex-5-enal (3.61 g, 17.2 mmol) (freshly azeotroped with dry benzene) and (R)-2-methylpropane-2-sulfinamide (2.08 g, 17.2 mmol) in tetrahydrofuran (100 mL) to give a yellow solution. Titanium(IV) ethoxide (36.0 mL, 34.3 mmol) was added dropwise, and the mixture was stirred at rt under nitrogen for 6 h. It was transferred to a stirred solution of brine (90 mL) and a white solid was formed. This was filtered through a plug of celite and washed with ethyl acetate. The eluent was concentrated to give a tan oil. The residue was purified by flash column chromatography up to 40% ethyl acetate/hexane afforded the desired product (3.94 g, 73% for 2 steps) as a light yellow oil: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.09 (d, J=4.52 Hz, 1H) 7.02-7.14 (m, 2H) 6.97 (d, J=8.28 Hz, 1H) 5.68-5.87 (m, 1H) 5.02 (d, J=13.05 Hz, 2H) 4.07-4.18 (m, 1H) 2.19 (dt, J=13.30, 6.65 Hz, 1H) 2.05-2.13 (m, 2H) 1.90-2.03 (m, 1H) 1.17 (s, 9H); 19F NMR (376 MHz, CHLOROFORM-d) δ ppm −137.55 (br. s., 1F) −142.03 (br. s., 1F); 13C NMR (101 MHz, CHLOROFORM-d) δ ppm 167.97 (s, 1C) 151.70-149.09 (m, 1C) 149.93-147.27 (m, 1C) 136.71 (d, J=9.25 Hz, 1C) 128.43 (d, J=9.25 Hz, I C) 122.99-124.42 (m, 1C) 115.88-115.68 (m, 1C) 115.37 (m, 1C) 109.63 (s, 1C) 56.77 (s, 1C) 43.94 (d, J=12.33 Hz, 1C) 30.83 (s, 1C) 30.40 (s, 1C) 21.96 (d, J=5.39 Hz, 3C).

Workup

  1. customto give a yellow solution
  2. customa white solid was formed
  3. filtrationThis was filtered through a plug of celite
  4. washwashed with ethyl acetate
  5. concentrationThe eluent was concentrated
  6. customto give a tan oil
  7. customThe residue was purified by flash column chromatography up to 40% ethyl acetate/hexane

Sources & evidence

ORD record
ord-8c7f594a708046a394b0fa1c9a24e69f
Source dataset
uspto-grants-2014_06
Patent number
US08748429B2

Reaction notes

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