Ethyl Acetate → N-(6-Bromo-5',6'-dihydro-4'H-spiro[chromene-2,3'-pyran]-4(3H)-ylidene)-2-methylpropane-2-sulfinamide

HRID 539354Notes

Reaction equation

HRID 539354 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1([CH2:12][CH2:11][CH2:10][O:9][CH2:8]1)[CH2:6][C:5]2=O.[CH3:18][C:19]([S:22]([NH2:24])=[O:23])([CH3:21])[CH3:20].CCOC(C)=O.C([O-])(O)=O.[Na+]>CN1C2C(N=C(N)NC=2NCC1CNC1C=CC(C(NC(C(O)=O)CCC(O)=O)=O)=CC=1)=O.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1([CH2:12][CH2:11][CH2:10][O:9][CH2:8]1)[CH2:6][C:5]2=[N:24][S:22]([C:19]([CH3:21])([CH3:20])[CH3:18])=[O:23]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 3382465Tert-ButanesulfinamideHCID 584238236-Bromo-2',4',5',6'-tetrahydrospiro[chroman-2,3'-pyran]-4-one2×

Product 1

HCID 67979337N-(6-Bromo-5',6'-dihydro-4'H-spiro[chromene-2,3'-pyran]-4(3H)-ylidene)-2-methylpropane-2-sulfinamideYield 97%

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 178479889HCID 178479889, compoundSolvent

Procedure

6-Bromo-5′,6′-dihydro-4′H-spiro[chromene-2,3′-pyran]-4(3H)-one (Intermediate 26, 2.007 g, 6.75 mmol), 2-methylpropane-2-sulfinamide (1.228 g, 10.13 mmol) and titanium ethoxide (2.78 mL, 13.51 mmol) were dissolved in methyl THF (16 mL) and heated to reflux for 19 h. The reaction was left to cool down to r.t. when EtOAc (80 mL) and NaHCO3 (sat., 5 mL) were added under stirring. The mixture was let standing for 1 h. The organic phase was collected by filtration, dried over MgSO4 and concentrated. The crude product was purified by flash chromatography using a gradient of 0-50% EtOAc in heptane. The desired fractions were evaporated to give the title compound as a mixture of diastereomers in a ratio 1:1 as determined by NMR (2.63 g, 97% yield): 1H NMR (500 MHz, CDCl3) δ ppm 1.34 (s, 9H), 1.50-1.57 (m, 0.5H), 1.60-1.68 (m, 1H), 1.73 (m, 0.5H) 1.87-2.09 (m, 2H), 2.99 (d, 0.5H), 3.26 (d, 0.5H), 3.33 (d, 0.5H), 3.45-3.61 (m, 2H), 3.64 (d, 0.5H), 3.77-3.93 (m, 2H), 6.88-6.93 (m, 1H), 7.48 (dd, 1H), 7.98 (dd, 1H); MS (ES+) m/z 401.9 [M+H]+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 19 h
  3. waitThe reaction was left
  4. additionwere added
  5. filtrationThe organic phase was collected by filtration
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography
  9. customThe desired fractions were evaporated

Sources & evidence

ORD record
ord-9e093ea93e9c489a96d5ca3e47b79ab5
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

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