2,6-Lutidine → [2-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-ethoxymethyl]-phosphonic Acid
Reaction equation
C([O:4][P:5]([CH2:11][O:12][CH2:13][CH2:14][C:15]1[C:16]([O:28]CC[Si](C)(C)C)=[C:17]2[C:21](=[C:22]([CH3:26])[C:23]=1[O:24][CH3:25])[CH2:20][O:19][C:18]2=[O:27])(=[O:10])[O:6]C(C)C)(C)C.N1C(C)=CC=CC=1C.C[Si](Br)(C)C>C(#N)C>[OH:28][C:16]1[C:15]([CH2:14][CH2:13][O:12][CH2:11][P:5](=[O:4])([OH:10])[OH:6])=[C:23]([O:24][CH3:25])[C:22]([CH3:26])=[C:21]2[C:17]=1[C:18](=[O:27])[O:19][CH2:20]2Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of {2-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-ethoxymethyl}-phosphonic acid diisopropyl ester (7.5 mg, 0.014 mmol) in acetonitrile (2 mL) and 2,6-lutidine (25 μL, 0.21 mmol) was added trimethylsilyl bromide (27 μL, 0.21 mmol) at room temperature. The reaction was allowed to proceed for 18 hours when completion of the reaction was indicated by LCMS. The reaction was quenched by addition of MeOH and concentration. The residue was purified by reverse-phase HPLC using a C18 column. The collected product was dispensed in a solution of 10% TFA/CH2Cl2 to assure complete cleavage of the TMSE group. The reaction mixture was lyophilized to provide the desired product. 1H NMR (300 MHz, CD3OD) δ 2.12 (s, 3H), 2.98 (t, 2H, J=7 Hz), 3.66-3.76 (m, 4H), 3.78 (s, 3H), 5.21 (s, 2H); MS (m/z) 331 [M−H]−.
Workup
- customThe reaction was quenched by addition of MeOH and concentration
- customThe residue was purified by reverse-phase
Sources & evidence
- ORD record
- ord-d2ce76bbaf5c4299af65f2f4a4cff059
- Source dataset
- uspto-grants-2008_11
- Patent number
- US07452901B2
Reaction notes
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