Acetone → 2-[2,6-Dichloro-9-(tetrahydro-2H-pyran-2-yl)-8-purinyl]-2-propanol

HRID 334158Notes

Reaction equation

[Li]CCCC.[Cl:6][C:7]1[N:15]=[C:14]2[C:10]([N:11]=[CH:12][N:13]2[CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[C:9]([Cl:22])[N:8]=1.CN(CCN(C)C)C.[CH3:31][C:32]([CH3:34])=[O:33]>C1COCC1>[Cl:6][C:7]1[N:15]=[C:14]2[C:10]([N:11]=[C:12]([C:32]([OH:33])([CH3:34])[CH3:31])[N:13]2[CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[C:9]([Cl:22])[N:8]=1

Participants

Conditions

Temperature: -78 °C

Procedure

BuLi (20 mL, 40.0 mmol, 2 M in pentane) was added dropwise to a solution of 2,6-dichloro-9-(tetrahydro-pyran-2-yl)-9H-purine (8.0 g, 29.3 mmol) and TMEDA (6.4 mL, 42.4 mmol) in anhydrous THF (100 mL) at −78° C. The resulting dark solution was stirred at −78° C. for 45 min, then acetone (4 mL, 54.5 mmol) was added and the reaction mixture was stirred at −78° C. for 30 min, then at RT for 30 min. The reaction mixture was quenched with water and extracted with ethyl acetate. The combined organic extracts were dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, 0 to 20% ethyl acetate in cyclohexane) affording 2-[2,6-Dichloro-9-(tetrahydro-pyran-2-yl)-9H-purin-8-yl]-propan-2-ol as a dark solid (6.0 g, 62%). 1H NMR (400 MHz, CDCl3); δ 6.19 (1H, dd, J=11.2, 2.8 Hz), 4.26 (1H, m), 3.77 (1H, m), 2.87 (1H, m), 2.09 (1H, m), 1.90-1.71 (11H, m).

Workup

stirringthe reaction mixture was stirred at −78° C. for 30 min
waitat RT for 30 min
customThe reaction mixture was quenched with water
extractionextracted with ethyl acetate
dry with materialThe combined organic extracts were dried (MgSO4)
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (SiO2, 0 to 20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record: ord-e3f67534f09b49f090b60438f6af5945
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883799B2

Reaction notes

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