p-Toluenesulfonic acid monohydrate → HCID 86689941, compound

HRID 1847840Notes

Reaction equation

HRID 1847840 reaction equation
C(C1N(CC2COC(C)(C)O2)C2C(C=1)=CC([NH:14][C:15]([C:17]1([C:20]3[CH:30]=[CH:29][C:23]4[O:24][C:25]([F:28])([F:27])[O:26][C:22]=4[CH:21]=3)[CH2:19][CH2:18]1)=[O:16])=CC=2)(C)(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.O>[F:28][C:25]1([F:27])[O:24][C:23]2[CH:29]=[CH:30][C:20]([C:17]3([C:15]([NH2:14])=[O:16])[CH2:19][CH2:18]3)=[CH:21][C:22]=2[O:26]1

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 24763548HCID 24763548, compound

Product 1

HCID 86689941HCID 86689941, compoundYield 163.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of N-(2-tert-butyl-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-indol-5-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (1.28 g, 2.43 mmol) in methanol (34 mL) and water (3.7 mL) was added para-toluenesulfonic acid-hydrate (1.87 g, 9.83 mmol). The reaction mixture was stirred and heated at 80° C. for 25 minutes. The solvent was evaporated under reduced pressure. The crude product was dissolved in ethyl acetate. The organic layer was washed with saturated aqueous NaHCO3 (2×10 mL) and brine (2×10 mL). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/hexane=13/7) to give N—((R)-2-tert-butyl-1-2,3-dihydroxypropyl)-1H-indol-5-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (0.96 g, 81%). 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J=2 Hz, 1H), 7.31 (dd, J=2, 8 Hz, 1H), 7.27 (dd, J=2, 8 Hz, 1H), 7.23 (d, J=8 Hz, 1H), 7.14 (d, J=8 Hz, 1H), 7.02 (br s, 1H), 6.96 (dd, J=2, 8 Hz, 1H), 6.23 (s, 1H), 4.35 (dd, J=8, 15 Hz, 1H), 4.26 (dd, J=4, 15 Hz, 1H), 4.02-3.95 (m, 1H), 3.60 (dd, J=4, 11 Hz, 1H), 3.50 (dd, J=5, 11 Hz, 1H), 1.75 (q, J=8 Hz, 3H), 1.43 (s, 9H), 1.14 (q, J=8 Hz, 3H).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionThe crude product was dissolved in ethyl acetate
  3. washThe organic layer was washed with saturated aqueous NaHCO3 (2×10 mL) and brine (2×10 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel (ethyl acetate/hexane=13/7)

Sources & evidence

ORD record
ord-c7fa25d0ccf34a959551cea5471ffa33
Source dataset
uspto-grants-2015_02
Patent number
US08952049B2

Reaction notes

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