Sulfuric Acid → [N(E),S(R)]-N-[1-(5-Bromo-2-fluorophenyl)ethylidene]-2-methyl-2-propanesulfinamide

HRID 920186Notes

Reaction equation

HRID 920186 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([C:8](=O)[CH3:9])[CH:7]=1.[CH3:12][C:13]([S@:16]([NH2:18])=[O:17])([CH3:15])[CH3:14].C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+].S(=O)(=O)(O)O.C([O-])([O-])=O.[Na+].[Na+]>O1CCCC1.CC(OC)(C)C.[Cl-].[Na+].O.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC.CCCCCCC.C(OCC)(=O)C.CCCCC>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6](/[C:8](=[N:18]/[S@@:16]([C:13]([CH3:15])([CH3:14])[CH3:12])=[O:17])/[CH3:9])[CH:7]=1

Participants

12

Reactant 5

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 9855836Potassium sodium tartarateHCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 226074761-(5-Bromo-2-fluorophenyl)ethanone

Product 1

HCID 87126877[N(E),S(R)]-N-[1-(5-Bromo-2-fluorophenyl)ethylidene]-2-methyl-2-propanesulfinamideYield 87.5%

Reagents, catalysts & solvents 6

HCID 76524Titanium tetraethoxideCatalystHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolventHCID 21899848Ethylacetate heptaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
75 °C

Procedure

Commercially available 1-(5-bromo-2-fluorophenyl)ethanone (140 g, 645 mmol, Eq: 1.0) [CAS No. 477-89-3], (R)-2-methylpropane-2-sulfinamide (78.2, 645 mmol, Eq: 1.0) and titanium(IV) ethoxide (221 g, 204 ml, 968 mmol, Eq: 1.5) were dissolved in tetrahydrofuran (1.19 l) and the mixture heated to 75° C. and stirred at this temperature overnight. The mixture was cooled to 50° C., sat. potassium sodium tartrate solution (1.17 l, 2.58 mol, Eq: 4) was added and the mixture stirred at this temperature for 1.5 hours. The mixture was diluted with TBME, the layers separated, the organic layer washed with sulfuric acid (0.05 M, 2.36 l, 118 mmol, Eq: 0.183), sat. Na2CO3-solution (645 ml, 645 mmol, Eq: 1.00) and brine, dried over Na2SO4 and the solvent evaporated leaving an dark orange solid, which was purified by trituration with n-heptane to give the first batch (144.7 g) as an off-white solid. From the mother liquor another batch (23.0 g) was obtained by trituration with pentane, yet another batch was obtained by silica gel column chromatography with n-heptane/ethyl acetate. Total yield of (R,E)-N-(1-(5-bromo-2-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide (180.7 g, 564 mmol, 87.5% yield) as an off-white solid. MS (ISP): m/z=320.3 [M+H]+ and 322.0 [M+2+H]+.

Workup

  1. temperatureThe mixture was cooled to 50° C.
  2. stirringthe mixture stirred at this temperature for 1.5 hours
  3. customthe layers separated
  4. dry with materialdried over Na2SO4
  5. customthe solvent evaporated
  6. customleaving an dark orange solid, which
  7. customwas purified by trituration with n-heptane
  8. customto give the first batch (144.7 g) as an off-white solid

Sources & evidence

ORD record
ord-cbaefd2b45164cd797459d9641b08424
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

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