Ethyl Acetate → N-(5'-Bromo-4,4-difluorospiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide

HRID 539340Notes

Reaction equation

HRID 539340 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]3)[C:8]2=O)=[CH:4][CH:3]=1.[CH3:19][C:20]([S:23]([NH2:25])=[O:24])([CH3:22])[CH3:21].CCOC(C)=O.C([O-])(O)=O.[Na+]>CCCCCCC.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[Br:1][C:2]1[CH:10]=[C:9]2[C:5](=[CH:4][CH:3]=1)[CH2:6][C:7]1([CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]1)[C:8]2=[N:25][S:23]([C:20]([CH3:22])([CH3:21])[CH3:19])=[O:24]

Participants

7

Reactant 4

HCID 8857Ethyl Acetate2×HCID 516892Sodium BicarbonateHCID 3382465Tert-ButanesulfinamideHCID 581972726'-bromo-4,4-difluorospiro[cyclohexane-1,2'-inden]-1'(3'H)-one2×

Product 1

HCID 67979525N-(5'-Bromo-4,4-difluorospiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamideYield 31.3%

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 8900HeptaneSolvent

Conditions

Temperature
120 °C

Procedure

6′-Bromo-4,4-difluorospiro[cyclohexane-1,2′-inden]-1′(3′H)-one (Intermediate 11, 819 mg, 2.60 mmol), 2-methylpropane-2-sulfinamide (630 mg, 5.20 mmol) and titanium ethoxide (1.874 mL, 9.10 mmol) were dissolved in 2-Me THF (9 mL) and heated to 120° C. with MW for 1 h. EtOAc (20 mL) and NaHCO3 (aq., sat, 2 mL) were added under stirring. The mixture was left to stand without stirring for 1 h. The organic phase was collected by filtration, dried over MgSO4 and concentrated. Flash chromatography with a gradient of 0-50% EtOAc in n-heptane gave the title compound (340 mg, 31% yield). 1 H NMR (500 MHz, DMSO-d6) δ ppm 1.25 (s, 9 H), 1.56-1.71 (m, 2 H), 2.10 (br. s., 6 H), 3.12 (s, 2 H), 7.49 (d, 1 H), 7.81 (dd, 1 H), 8.43-8.63 (m, 1 H). MS (ES+) m/z 418 [M+H]+.

Workup

  1. waitThe mixture was left
  2. stirringwithout stirring for 1 h
  3. filtrationThe organic phase was collected by filtration
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-e46d0cf3e6d745b9a9771f0d2829cefc
Source dataset
uspto-grants-2014_10
Patent number
US08865911B2

Reaction notes

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