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

HRID 540730Notes

Reaction equation

HRID 540730 reaction equation
C([O:3][P:4]([CH2:9][CH2:10][NH:11][C:12](=[O:39])[CH2:13][CH2:14][C:15]([CH3:38])=[CH:16][CH2:17][C:18]1[C:19]([O:31]CC[Si](C)(C)C)=[C:20]2[C:24](=[C:25]([CH3:29])[C:26]=1[O:27][CH3:28])[CH2:23][O:22][C:21]2=[O:30])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C.N1C(C)=CC=CC=1C>C(#N)C>[OH:31][C:19]1[C:18]([CH2:17][CH:16]=[C:15]([CH3:38])[CH2:14][CH2:13][C:12]([NH:11][CH2:10][CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[O:39])=[C:26]([O:27][CH3:28])[C:25]([CH3:29])=[C:24]2[C:20]=1[C:21](=[O:30])[O:22][CH2:23]2

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 76113BromotrimethylsilaneHCID 76541035(2-{6-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoylamino}-ethyl)-phosphonic acid diethyl ester

Product 1

HCID 67011281{2-[6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-4-methyl-hex-4-enoylamino]-ethyl}-phosphonic AcidYield 29%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (2-{6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoylamino}-ethyl)-phosphonic acid diethyl ester (36.6 mg, 0.063 mmol) in acetonitrile (1 mL) was added TMSBr (81 μL, 0.63 mmol) followed by 2,6-lutidine (73 μL, 0.63 mmol). The reaction was allowed to proceed overnight when it was completed as judged by LCMS. The reaction mixture was quenched with MeOH and concentrated to dryness. The residue was purified by preparative reverse-phase HPLC to afford 5.8 mg (29%) of desired product as a white solid. 1H NMR (300 MHz, CD3OD) δ 1.80 (s, 3H), 2.14 (m, 5H), 2.25 (m, 4H), 3.35 (m, 2H), 3.38-3.38 (m, 2H), 3.75 (s, 3H), 5.23 (s, 3H) ppm; 31P (121.4 MHz, CD3OD) δ 26.03 ppm; MS (m/z) 426 [M−H]−, 428 [M+H]+.

Workup

  1. customThe reaction mixture was quenched with MeOH
  2. concentrationconcentrated to dryness
  3. customThe residue was purified by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-0d1135978d084541a1349664b6c025c8
Source dataset
uspto-grants-2014_10
Patent number
US08871785B2

Reaction notes

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