HCID 86700136, compound → HCID 86700137, compound

HRID 879338Notes

Reaction equation

HRID 879338 reaction equation
[Br:1][C:2]1[S:3][C:4]2[C:10](=[O:11])/[C:9](=[CH:12]/[C:13]([O:15][CH2:16][CH3:17])=[O:14])/[CH:8]([CH3:18])[CH2:7][C:5]=2[N:6]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([Mg]Br)=[CH:22][CH:21]=1>C1COCC1>[Br:1][C:2]1[S:3][C:4]2[C:10]([C:23]3[CH:24]=[CH:25][C:20]([Cl:19])=[CH:21][CH:22]=3)([OH:11])/[C:9](=[CH:12]/[C:13]([O:15][CH2:16][CH3:17])=[O:14])/[CH:8]([CH3:18])[CH2:7][C:5]=2[N:6]=1

Participants

4

Reactant 2

HCID 86700136HCID 86700136, compoundHCID 178478191HCID 178478191, compound

Product 1

HCID 86700137HCID 86700137, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-65 °C

Procedure

A 3-liter flask equipped with a mechanical stirrer, addition funnel, and nitrogen inlet was charged with (E)-ethyl 2-(2-bromo-5-methyl-7-oxo-4,5-dihydrobenzo[d]thiazol-6(7H)-ylidene)acetate (24.1 g, 73 mmol, 1.0 equiv) and then diluted with THF (800 mL). To the resulting solution was added 0.6M LaCl3.2LiCl (243 mL, 146 mmol, 2.0 equiv) and then the reaction mixture was cooled to −65° C. by the aid of a dry-ice acetone bath. The addition funnel was then charged with 1.0M 4-chlorophenylmagnesium bromide (146 mL, 146 mmol, 2.0 equiv) and then slowly added to the reaction mixture over a 25 minute period. Upon completion of the addition, TLC analysis showed full consumption of the starting material (TLC of the starting material in 20% EtOAc/Hex has Rf=0.50; TLC of the product in 20% EtOAc/Hex has Rf=0.38), and the reaction was quenched with saturated NH4Cl (100 mL) and then diluted with EtOAc (1 L) and H2O (1.5 L). The cooling bath was removed and the mixture was allowed to warm to room temperature with stirring. The layers were separated and the aqueous extract was washed with EtOAc (1 L). The combined organics were dried over Na2SO4, filtered through a small plug of silica gel eluting with EtOAc, and then concentrated in vacuo. The resulting crude residue was chromatographed using a 330 g RediSep normal phase silica gel cartridge (EtOAc/Hex, 5%→15%) on a CombiFlash system to afford desired product. TLC (20% EtOAc/Hex) Rf=0.38; 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J=8.6 Hz, 2H), 7.26 (d, J=8.6 Hz, 2H), 5.62 (s, 1H), 4.57-4.40 (m, 1H), 4.22-4.04 (m, 2H), 3.03 (qd, J=16.6, 3.8 Hz, 2H), 2.61 (br s, 1H), 1.38 (d, J=7.2 Hz, 3H), 1.25 (t, J=7.1 Hz, 3H).

Workup

  1. customA 3-liter flask equipped with a mechanical stirrer, addition funnel, and nitrogen inlet
  2. additionslowly added to the reaction mixture over a 25 minute period
  3. additionUpon completion of the addition, TLC analysis
  4. customconsumption of the starting material (TLC of the starting material in 20% EtOAc/Hex
  5. customwas quenched with saturated NH4Cl (100 mL)
  6. additiondiluted with EtOAc (1 L) and H2O (1.5 L)
  7. customThe cooling bath was removed
  8. temperatureto warm to room temperature
  9. customThe layers were separated
  10. extractionthe aqueous extract
  11. washwas washed with EtOAc (1 L)
  12. dry with materialThe combined organics were dried over Na2SO4
  13. filtrationfiltered through a small plug of silica gel eluting with EtOAc
  14. concentrationconcentrated in vacuo
  15. customThe resulting crude residue was chromatographed

Sources & evidence

ORD record
ord-78d26c9df0934770ae3c8d52d8a97a46
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

Loading…