tert-Butanol → HCID 57818921, compound

HRID 1500028Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])[C:5]([F:17])=[CH:4][N:3]=1.[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][OH:24])=[CH:21][CH:20]=1.CC([O-])(C)C.[K+].CC(O)(C)C>C1COCC1>[F:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[CH2:9][NH:8][C:6]1[C:5]([F:17])=[CH:4][N:3]=[C:2]([O:24][CH2:23][C:22]2[CH:25]=[CH:26][C:19]([F:18])=[CH:20][CH:21]=2)[N:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of (2-chloro-5-fluoropyrimidin-4-yl)-(2-fluorobenzyl)amine* (0.103 g, 0.40 mmol) in 5 mL of dry THF was treated with 4-fluorobenzylalcohol (0.062 g, 0.49 mmol) and a 1.0 M solution of KOtBu in tBuOH (0.4 mL, 0.4 mmol). The mixture was heated at 80° C. in a sealed vial for 18 h, partitioned between CH2Cl2 and water, and the organic phase was washed with brine, dried over Na2SO4, and filtered. The solvent was removed under reduced pressure and the residue purified by flash column chromatography (SiO2, 10→20% EtOAc/petroleum ether) to yield the title compound (0.157 g, 42%) as a white solid: mp 83-84° C.; 1H NMR (300 MHz, CDCl3) δ 7.83 (d, J=2.8, 1H), 7.45-7.27 (m, 5H), 7.15-6.96 (m, 5H), 5.37 (br s, 1H), 5.29 (s, 3H), 4.74 (d, J=5.9, 3H); MS (ESI) m/z 346 (M+H)+. *Singh, R.; Argade, A.; Payan, D. G.; Clough, J.; Keim, H.; Sylvain, C.; Li, H.; Bhamidipati, S., WO 2004014382 A1 20040219

Workup

custompartitioned between CH2Cl2 and water
washthe organic phase was washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
customThe solvent was removed under reduced pressure
customthe residue purified by flash column chromatography (SiO2, 10→20% EtOAc/petroleum ether)

Sources & evidence

ORD record: ord-6fac3538aec9455ab7a729c8577aa8dd
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09204653B2

Reaction notes

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