Hydrochloric Acid → trans-({3-[(5-Bromo-6-phenylfuro[2,3-d]pyrimidin-4-yl)oxy]cyclohexyl}oxy)acetic acid tert-butyl ester

HRID 2189058Notes

Reaction equation

[Br:1][C:2]1[C:10]2[C:9]([O:11][C@H:12]3[CH2:17][CH2:16][CH2:15][C@H:14]([OH:18])[CH2:13]3)=[N:8][CH:7]=[N:6][C:5]=2[O:4][C:3]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[OH-].[Na+].[C:27]([O:31][C:32](=[O:35])[CH2:33]Br)([CH3:30])([CH3:29])[CH3:28].Cl>C1(C)C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O>[C:27]([O:31][C:32](=[O:35])[CH2:33][O:18][C@H:14]1[CH2:15][CH2:16][CH2:17][C@H:12]([O:11][C:9]2[C:10]3[C:2]([Br:1])=[C:3]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[O:4][C:5]=3[N:6]=[CH:7][N:8]=2)[CH2:13]1)([CH3:30])([CH3:29])[CH3:28]

Participants

Conditions

Temperature: 60 °C

Procedure

Add a solution of 625 mg (1.606 mmol) of cis/trans-3-[(5-bromo-6-phenylfuro[2,3-d]pyrimidin-4-yl)oxy]cyclohexanol in 3 ml of toluene to a mixture of 2 ml of toluene and 1.28 g of 50% sodium hydroxide solution (16.05 mmol). Then add 54.5 mg (0.16 mmol) of tetra-n-butylammonium hydrogen sulphate and 626 mg (3.21 mmol) of bromoacetic acid tert-butyl ester to the biphasic mixture, and stir the reaction mixture vigorously at 60° C. for 3 h. Then add to water and neutralize with conc. hydrochloric acid. Extract the aqueous phase three times with ethyl acetate, combine the organic phases and dry over magnesium sulphate. The residue is purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 10:1→8:1). 592 mg of the target compound are obtained (73.2% of theory).

Workup

extractionExtract the aqueous phase three times with ethyl acetate
dry with materialdry over magnesium sulphate
customThe residue is purified by chromatography on silica gel (eluent: cyclohexane/ethyl acetate 10:1→8:1)

Sources & evidence

ORD record: ord-11a98fcea77f48cb899992fea94b1983
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08324222B2

Reaction notes

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