HCID 87194381, compound → HCID 86635616, compound

HRID 2383542Notes

Reaction equation

HRID 2383542 reaction equation
[CH3:1][C:2]([S:5](/[N:7]=[CH:8]/[C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[CH:11][N:10]=1)=O)([CH3:4])[CH3:3].[CH:21]([Mg]Br)=[CH2:22]>O1CCCC1>[C:2]([S:5][NH:7][C@@H:8]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[CH:11][N:10]=1)[CH:21]=[CH2:22])([CH3:4])([CH3:3])[CH3:1]

Participants

4

Reactant 2

HCID 87194381HCID 87194381, compoundHCID 178418507HCID 178418507, compound2×

Product 1

HCID 86635616HCID 86635616, compoundYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a mixture of 2-methyl-N-{(1E)-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylidene}propane-2-sulfinamide (10.0 g, 32.4 mmol) and tetrahydrofuran (150 ml) at −78° C. was added dropwise 1.0M vinylmagnesium bromide in tetrahydrofuran (58.4 ml, 58.4 mmol), maintaining temperature during addition below −70° C. Reaction was stirred at −78° C. for an hour. To complete reaction, an additional amount of 1.0M vinylmagnesium bromide (19.4 ml, 19.4 mmol) was required. The reaction was then quenched by pouring mixture into a cold solution of saturated NH4Cl (800 ml) and ethyl acetate (600 ml) with vigorous stirring at 0° C. Layers were separated and organic extracts were combined, dried over Na2SO4, filtered and concentrated in vacuum. The resulting brown oil was purified by flash chromatography (Si2O, 25-100% ethyl acetate in hexanes, gradient) to give 2-{(1R)-1-[(tert-butylthio)amino]prop-2-enyl}-5-(2,2,2-trifluoroethoxy)pyridine as a white solid (8.10 g, 73.5%). 1H NMR (400 MHz, CDCl3) 8.30 (d, J=2.8 Hz, 1H), 7.28 (m, 2H), 5.92-5.83 (m, 1H), 5.34 (dd, J=16 Hz and 33 Hz, 2H), 5.01 (m, 1H), 4.99 (bs, 1H), 4.39 (q, J=8.0 Hz, 2H), 1.28 (s, 9H); MS(Electrospray): m/z 337.1 (M+H).

Workup

  1. temperaturemaintaining temperature
  2. additionduring addition below −70° C
  3. customReaction
  4. customTo complete reaction
  5. customThe reaction was then quenched
  6. additionby pouring mixture into a cold solution of saturated NH4Cl (800 ml) and ethyl acetate (600 ml)
  7. stirringwith vigorous stirring at 0° C
  8. customLayers were separated
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuum
  12. customThe resulting brown oil was purified by flash chromatography (Si2O, 25-100% ethyl acetate in hexanes, gradient)

Sources & evidence

ORD record
ord-ae7e452bea354ddfaac792a8792b8fbb
Source dataset
uspto-grants-2012_09
Patent number
US08263627B2

Reaction notes

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