Water → (+/-)-cis-({3-[(6-Phenylfuro[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}oxy)acetic acid tert-butyl ester

HRID 2189037Notes

Reaction equation

[C:1]1([C:7]2[O:23][C:10]3[N:11]=[CH:12][N:13]=[C:14]([NH:15][C@@H:16]4[CH2:21][CH2:20][CH2:19][C@H:18]([OH:22])[CH2:17]4)[C:9]=3[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].[C:26]([O:30][C:31](=[O:34])[CH2:32]Br)([CH3:29])([CH3:28])[CH3:27].O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C1COCC1>[C:26]([O:30][C:31](=[O:34])[CH2:32][O:22][C@H:18]1[CH2:19][CH2:20][CH2:21][C@@H:16]([NH:15][C:14]2[C:9]3[CH:8]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[O:23][C:10]=3[N:11]=[CH:12][N:13]=2)[CH2:17]1)([CH3:29])([CH3:28])[CH3:27]

Participants

Conditions

Temperature: 70 °C

Procedure

At 40° C., add approx. 0.06 mmol of tetrabutylammonium hydrogensulphate and a solution of 200 mg (0.646 mmol) of (+/−)-cis-3-[(6-phenylfuro[2,3-d]pyrimidin-4-yl)amino]cyclohexanol in 0.5 ml of toluene and 0.1 ml of THF to a mixture of 517 mg of 50% sodium hydroxide solution (6.5 mmol) and 0.5 ml of toluene. Admix the resulting mixture with 0.19 ml (1.29 mmol) of bromoacetic acid tert-butyl ester with vigorous stirring and heat it to 70° C. After 2 h, cool the mixture and add it to water. Extract three times with dichloromethane, wash the combined organic phases with saturated sodium chloride solution and concentrate under reduced pressure. After preparative RP-HPLC (eluent: acetonitrile/water), 152 mg (55.5% of theory) of the target product are isolated from the crude product.

Workup

temperaturecool the mixture
extractionExtract three times with dichloromethane
washwash the combined organic phases with saturated sodium chloride solution
concentrationconcentrate under reduced pressure

Sources & evidence

ORD record: ord-b14def8bf2cc47f3aa2c0a7633a384bc
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08324222B2

Reaction notes

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