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

HRID 910485Notes

Reaction equation

HRID 910485 reaction equation
C[O:2][P:3]([CH:7]=[CH:8][C:9]([CH3:26])=[CH:10][CH2:11][C:12]1[C:13]([OH:25])=[C:14]2[C:18](=[C:19]([CH3:23])[C:20]=1[O:21][CH3:22])[CH2:17][O:16][C:15]2=[O:24])(=[O:6])[O:4]C.N1C(C)=CC=CC=1C.C[Si](Br)(C)C>C(#N)C>[OH:25][C:13]1[C:12]([CH2:11][CH:10]=[C:9]([CH3:26])[CH:8]=[CH:7][P:3](=[O:2])([OH:6])[OH:4])=[C:20]([O:21][CH3:22])[C:19]([CH3:23])=[C:18]2[C:14]=1[C:15](=[O:24])[O:16][CH2:17]2

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 76113BromotrimethylsilaneHCID 76548182[5-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-3-methyl-penta-1,3-dienyl]-phosphonic acid dimethyl ester

Product 1

HCID 75023224[5-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-3-methyl-penta-1,3-dienyl]-phosphonic acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of [5-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-3-methyl-penta-1,3-dienyl]-phosphonic acid dimethyl ester 157B (22 mg, 0.057 mmol) and 2,6-lutidine (0.22 mL, 1.71 mmol) in acetonitrile was added trimethylsilyl bromide (0.183 mL, 1.71 mmol) at 0° C. The mixture was allowed to warm to room temperature and stirred for 1 hour. The reaction was quenched with methanol at 0° C., and the resulting mixture was concentrated. The residue was purified by preparative reverse-phase HPLC to afford, after removal of the solvent, [5-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-3-methyl-penta-1,3-dienyl]-phosphonic acid 157C as a solid (13 mg, 65%); 1H NMR (300 MHz, CD3OD) δ 1.91 (s, 3H), 2.10 (s, 3H), 3.55 (d, J=6.6 Hz, 2H), 3.75 (s, 3H), 5.2 (s, 2H), 5.6-5.8 (m, 2H), 6.9 (m, 1H) ppm.

Workup

  1. customThe reaction was quenched with methanol at 0° C.
  2. concentrationthe resulting mixture was concentrated
  3. customThe residue was purified by preparative reverse-phase HPLC
  4. customto afford
  5. customafter removal of the solvent, [5-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-3-methyl-penta-1,3-dienyl]-phosphonic acid 157C as a solid (13 mg, 65%)

Sources & evidence

ORD record
ord-190e977eabbd492b88a26778accd788e
Source dataset
uspto-grants-2011_09
Patent number
US08022083B2

Reaction notes

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