Hydrochloric Acid → trans-3-[(5-Bromo-6-phenylfuro[2,3-d]pyrimidin-4-yl)oxy]cyclohexanol

HRID 2189057Notes

Reaction equation

CO[CH2:3][CH2:4][O:5]C.[OH-:7].[Na+].[Br:9][C:10]1[C:18]2[C:17](Cl)=[N:16][CH:15]=[N:14][C:13]=2[O:12][C:11]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl>C1(C)C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O>[Br:9][C:10]1[C:18]2[C:17]([O:5][C@H:4]3[CH2:3][CH2:20][CH2:11][C@H:10]([OH:7])[CH2:18]3)=[N:16][CH:15]=[N:14][C:13]=2[O:12][C:11]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

Conditions

Temperature: 70 °C

Procedure

Dissolve 1.1 g (8.88 mmol) of cis/trans-cyclohexanediol at 70° C. in 10 ml of toluene and 5 ml of 1,2-dimethoxyethane and add 2.84 g of 50% sodium hydroxide solution (35.5 mmol). Add water until a biphasic reaction mixture forms. Add 120.6 mg (3.55 mmol) of tetra-n-butylammonium hydrogen sulphate and 1.10 g (3.55 mmol) of 5-bromo-4-chloro-6-phenylfuro[2,3-d]pyrimidine, and stir the mixture vigorously at 70° C. for 1 h. After cooling, add the reaction mixture to water and neutralize with conc. hydrochloric acid. Extract the aqueous phase three times with ethyl acetate. Combine the organic phases, wash with satd. sodium hydrogen sulphate solution, dry over magnesium sulphate and concentrate under reduced pressure. Purify the residue by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 5:1→3:1). 0.63 g of the title compound is obtained (45.6% of theory).

Workup

temperatureAfter cooling
extractionExtract the aqueous phase three times with ethyl acetate
washwash with satd
dry with materialsodium hydrogen sulphate solution, dry over magnesium sulphate
concentrationconcentrate under reduced pressure
customPurify the residue by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 5:1→3:1)

Sources & evidence

ORD record: ord-237552ed339e4e608b4411e6b098bc7c
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08324222B2

Reaction notes

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