3-Hydroxybenzyl alcohol → (3-(5-Bromopyrimidin-2-yloxy)phenyl)methanol

HRID 1666376Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].Cl[C:11]1[N:16]=[CH:15][C:14]([Br:17])=[CH:13][N:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[Br:17][C:14]1[CH:13]=[N:12][C:11]([O:1][C:2]2[CH:3]=[C:4]([CH2:5][OH:6])[CH:7]=[CH:8][CH:9]=2)=[N:16][CH:15]=1

Participants

Conditions

Temperature: 110 °C

Procedure

3-Hydroxybenzyl alcohol (1.50 g, 12.1 mmol) and 2-chloro-5-bromopyrimidine (2.57 g, 13.3 mmol) were suspended in DMSO (20 mL), treated with cesium carbonate (4.35 g, 13.4 mmol) and heated to 110° C. After 16 h, the reaction mixture was cooled and partitioned between water (200 mL) and heptane:ethyl acetate (1:1, 200 mL). The organic layer was separated and the aqueous was extracted again with heptane:ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica (20-70% EtOAc:heptane) to afford the title compound (0.790 g, 23% yield) as a light yellow oil. MS (APCI) M+1=281.0; 1H NMR (400 MHz, CDCl3) δ ppm 4.74 (s, 2H) 7.08-7.14 (m, 1H) 7.20-7.23 (m, 1H) 7.25-7.30 (m, 1H) 7.43 (t, J=7.80 Hz, 1H) 8.57 (s, 2H).

Workup

temperaturethe reaction mixture was cooled
custompartitioned between water (200 mL) and heptane:ethyl acetate (1:1, 200 mL)
customThe organic layer was separated
extractionthe aqueous was extracted again with heptane
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography on silica (20-70% EtOAc:heptane)

Sources & evidence

ORD record: ord-d14e7dfb05da4b40a2894284892ea3f8
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044052B2

Reaction notes

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