2,6-Lutidine → [2-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-ethoxymethyl]-phosphonic Acid

HRID 910509Notes

Reaction equation

HRID 910509 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]2

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 76113BromotrimethylsilaneHCID 57478687{2-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilany-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-ethoxymethyl}-phosphonic Acid Diisopropyl Ester

Product 1

HCID 59794464[2-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-ethoxymethyl]-phosphonic Acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

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 RP-HPLC using a C18 column. The collected product was dissolved in a solution of 10% TFA/CH2Cl2 to assure complete deprotection. 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) ppm; MS (m/z) 331 [M−H]−.

Workup

  1. customThe reaction was quenched by addition of MeOH and concentration
  2. customThe residue was purified by RP-HPLC
  3. dissolutionThe collected product was dissolved in a solution of 10% TFA/CH2Cl2

Sources & evidence

ORD record
ord-fac4412b9e3e44eea05793dd463da918
Source dataset
uspto-grants-2011_09
Patent number
US08022083B2

Reaction notes

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