Bromotrimethylsilane → {2-[2-Ethyl-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-but-2-enylamino]-ethyl}-phosphonic acid

HRID 2378830Notes

Reaction equation

HRID 2378830 reaction equation
C([O:3][P:4]([CH2:9][CH2:10][NH:11][CH2:12][C:13]([CH2:36][CH3:37])=[CH:14][CH2:15][C:16]1[C:17]([O:29]CC[Si](C)(C)C)=[C:18]2[C:22](=[C:23]([CH3:27])[C:24]=1[CH2:25][CH3:26])[CH2:21][O:20][C:19]2=[O:28])(=[O:8])[O:5]CC)C.C[Si](Br)(C)C>CN(C=O)C.C(Cl)Cl>[CH2:36]([C:13](=[CH:14][CH2:15][C:16]1[C:17]([OH:29])=[C:18]2[C:22](=[C:23]([CH3:27])[C:24]=1[CH2:25][CH3:26])[CH2:21][O:20][C:19]2=[O:28])[CH2:12][NH:11][CH2:10][CH2:9][P:4](=[O:3])([OH:8])[OH:5])[CH3:37]

Participants

5

Reactant 2

HCID 76113BromotrimethylsilaneHCID 72563629(2-{2-Ethyl-4-[6-ethyl-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-but-2-enyl amino}-ethyl)-phosphonic acid diethyl ester

Product 1

HCID 67010234{2-[2-Ethyl-4-(6-ethyl-4-hydroxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-but-2-enylamino]-ethyl}-phosphonic acidYield 44.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

(2-{2-Ethyl-4-[6-ethyl-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-but-2-enylamino}-ethyl)-phosphonic acid diethyl ester (24.9 mg, 0.045 mmol) was dissolved in DMF (0.5 mL) and DCM (0.5 mL). Trimethylsilyl bromide (68.7 mg, 0.449 mmol) was added and the reaction was stirred at room temperature. After 20 hours, the reaction was quenched with MeOH (0.15 mL). The solvents were evaporated in vacuo and the crude material was purified by RP-HPLC (eluent: water/MeCN). The product-containing fractions were combined and lyophilized to yield 8.0 mg of the free phosphonic acid [MS: 498 M++1].

Workup

  1. customthe reaction was quenched with MeOH (0.15 mL)
  2. customThe solvents were evaporated in vacuo
  3. customthe crude material was purified by RP-HPLC (eluent: water/MeCN)

Sources & evidence

ORD record
ord-b741e5b9111b4af59fd694655888291c
Source dataset
uspto-grants-2008_12
Patent number
US07470724B2

Reaction notes

Loading…