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

HRID 272178Notes

Reaction equation

HRID 272178 reaction equation
C([O:3][P:4]([CH2:9][NH:10][CH2:11][C:12]([CH3:35])=[CH: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:8])[O:5]CC)C.C[Si](Br)(C)C.N1C(C)=CC=CC=1C>CN(C=O)C>[OH:28][C:16]1[C:15]([CH2:14][CH:13]=[C:12]([CH3:35])[CH2:11][NH:10][CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[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 76541031({4-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enylamino}-methyl)-phosphonic acid diethyl ester

Product 1

HCID 67011097{[4-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enylamino]-methyl}-phosphonic AcidYield 39.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ({4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enylamino}-methyl)-phosphonic acid diethyl ester (20 mg, 0.038 mmol) in DMF (0.5 mL) was added TMSBr (49 μL, 0.38 mmol) and 2,6-lutidine (44 μL, 0.38 mmol). The solution was stirred at room temperature for 1 hour when it was quenched by addition of methanol. The product was purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, 0.1% TFA to provide 5.6 mg of the product as a white solid. 1H NMR (300 MHz, CD3OD and CDCl3) δ 1.93 (s, 3H), 2.13 (s, 3H), 2.94 (br d, 2H, J=11 Hz), 3.42-3.53 (m, 2H), 3.60 (s, 2H), 3.78 (s, 3H), 5.22 (s, 2H), 5.71 (br s, 1H) ppm; 31P (121.4 MHz, CDCl3) δ 8.5 ppm; MS (m/z) 372.2 [M+H]+, 743.2 [2M+H]+.

Workup

  1. customwas quenched by addition of methanol
  2. customThe product was purified by RP HPLC

Sources & evidence

ORD record
ord-e6c4be84a1994136bfb99149793abb76
Source dataset
uspto-grants-2008_11
Patent number
US07452901B2

Reaction notes

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