Methanol → N-(5-Bromo-2',3',5',6'-tetrahydrospiro[indene-2,4'-pyran]-3(1 H)-ylidene)-2-methylpropane-2-sulfinamide

HRID 1770943Notes

Reaction equation

HRID 1770943 reaction equation
[Br:1][C:2]1[CH:15]=[C:14]2[C:5]([CH2:6][C:7]3([C:13]2=O)[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)=[CH:4][CH:3]=1.[CH3:17][C:18]([S:21]([NH2:23])=[O:22])([CH3:20])[CH3:19].CO.C([O-])(O)=O.[Na+]>CC1CCCO1.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC.CCOC(C)=O>[Br:1][C:2]1[CH:15]=[C:14]2[C:5](=[CH:4][CH:3]=1)[CH2:6][C:7]1([CH2:12][CH2:11][O:10][CH2:9][CH2:8]1)[C:13]2=[N:23][S:21]([C:18]([CH3:20])([CH3:19])[CH3:17])=[O:22]

Participants

8

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 3382465Tert-ButanesulfinamideHCID 581981056-Bromo-2',3',5',6'-tetrahydrospiro[indene-2,4'-pyran]-1(3H)-one2×

Product 1

HCID 67979409N-(5-Bromo-2',3',5',6'-tetrahydrospiro[indene-2,4'-pyran]-3(1 H)-ylidene)-2-methylpropane-2-sulfinamideYield 35%

Reagents, catalysts & solvents 3

HCID 76524Titanium tetraethoxideCatalystHCID 73012-MethyltetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Titanium(IV) ethoxide (2.119 mL, 10.14 mmol) was added to a solution of 6-bromo-2′,3′,5′,6′-tetrahydrospiro[indene-2,4′-pyran]-1(3H)-one (Intermediate 10, 1.14 g, 4.05 mmol) and 2-methyl-2-propanesulfinamide (0.688 g, 5.68 mmol) in 2-methyl-tetrahydrofuran (12 mL) and the resulting mixture was stirred at 70° C. overnight. When cooled to r.t., MeOH (1.5 mL), sat. aq. NaHCO3 (5 mL) and EtOAc (10 mL) were added. The mixture was stirred for 1 h, then filtered through diatomaceous earth. The filter cake was washed with EtOAc (3×10 mL). The combined organics were washed with brine (30 mL), dried over MgSO4, filtered, concentrated and purified on a silica gel column eluted with 0-40% EtOAc in heptane to give 545 mg (35% yield) of the title compound; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.54 (br. s., 1H), 7.80 (dd, 1H), 7.51 (d, 1H), 3.88 (dd, 2H), 3.51 (m, 2H), 3.14 (s, 2H), 1.38 (m, 2H), 1.24 (m, 11H), MS (ES+) m/z 384 [M+H]+.

Workup

  1. temperatureWhen cooled to r.t.
  2. stirringThe mixture was stirred for 1 h
  3. filtrationfiltered through diatomaceous earth
  4. washThe filter cake was washed with EtOAc (3×10 mL)
  5. washThe combined organics were washed with brine (30 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified on a silica gel column
  10. washeluted with 0-40% EtOAc in heptane

Sources & evidence

ORD record
ord-9547d847553e44808006e04701a93a36
Source dataset
uspto-grants-2016_02
Patent number
US09248129B2

Reaction notes

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