Acetic Acid → (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

HRID 910552Notes

Reaction equation

HRID 910552 reaction equation
[CH2:1]([C:3](=[CH:6][CH2:7][C:8]1[C:9]([O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])=[C:10]2[C:14](=[C:15]([CH3:19])[C:16]=1[CH2:17][CH3:18])[CH2:13][O:12][C:11]2=[O:20])[CH:4]=O)[CH3:2].C(O)(=O)C(O)=O.[CH2:34]([O:36][P:37]([CH2:42][CH2:43][NH2:44])(=[O:41])[O:38][CH2:39][CH3:40])[CH3:35].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN(C=O)C>[CH2:39]([O:38][P:37]([CH2:42][CH2:43][NH:44][CH2:4][C:3]([CH2:1][CH3:2])=[CH:6][CH2:7][C:8]1[C:9]([O:21][CH2:22][CH2:23][Si:24]([CH3:25])([CH3:27])[CH3:26])=[C:10]2[C:14](=[C:15]([CH3:19])[C:16]=1[CH2:17][CH3:18])[CH2:13][O:12][C:11]2=[O:20])(=[O:41])[O:36][CH2:34][CH3:35])[CH3:40]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2733595Diethyl (2-aminoethyl)phosphonate oxalateHCID 5049666Sodium triacetoxyborohydrideHCID 765410332-Ethyl-4-[6-ethyl-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-but-2-enal

Product 1

HCID 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 esterYield 66.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Ethyl-4-[6-ethyl-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-but-2-enal (26.6 mg, 0.068 mmol) and aminoethylphosphonic acid diethylester oxalate salt (20.4 mg, 0.075 mmol) were dissolved in DMF (0.8 mL). Acetic acid (20.5 mg, 0.342 mmol) was added, followed by sodium triacetoxyborohydride (27.6 mg, 0.137 mmol). After 8 hrs, the crude reaction mixture was purified by RP-HPLC (eluent: water/MeCN) to provide 24.9 mg (65%) of the desired product after lyophilization. 1H NMR (300 MHz, CDCl3): δ=0.05 (s, 9H), 1.10-1.24 (m, 8H), 1.35 (t, J=7.5 Hz, 6H), 2.19 (s, 3H), 2.23 (m, 2H), 2.35 (q, J=7.8 Hz, 2H), 2.70 (q, J=7.2 Hz, 2H), 3.25 (m, 2H), 3.56 (m, 4H), 4.15 (m, 4H), 4.29 (m, 2H), 5.15 (s, 2H), 5.47 (m, 1H) ppm; 31P NMR (121 MHz, CDCl3): δ=27.71 ppm; MS=554 [M++1].

Workup

  1. customthe crude reaction mixture
  2. customwas purified by RP-HPLC (eluent: water/MeCN)

Sources & evidence

ORD record
ord-ef9631e9fbac4384b20af8390042a217
Source dataset
uspto-grants-2011_09
Patent number
US08022083B2

Reaction notes

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