Hexamethyldisilazane → HCID 22717883, compound

HRID 1368879Notes

Reaction equation

HRID 1368879 reaction equation
[CH3:1][CH:2]([CH3:18])[CH:3]([PH:15](=[O:17])[OH:16])[NH:4][C:5](=[O:14])[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C[Si](C)(C)N[Si](C)(C)C.[CH2:28]([O:35][C:36]([NH:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43](=[CH2:49])[C:44]([O:46][CH2:47][CH3:48])=[O:45])=[O:37])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[CH2:28]([O:35][C:36]([NH:38][CH2:39][CH2:40][CH2:41][CH2:42][CH:43]([CH2:49][P:15]([CH:3]([NH:4][C:5](=[O:14])[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH:2]([CH3:18])[CH3:1])([OH:16])=[O:17])[C:44]([O:46][CH2:47][CH3:48])=[O:45])=[O:37])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

4

Reactant 3

HCID 13838HexamethyldisilazaneHCID 22717973HCID 22717973, compoundHCID 178449450HCID 178449450, compound

Product 1

HCID 22717883HCID 22717883, compoundYield 41%

Conditions

Temperature
110 °C

Procedure

The 2-methyl-1-(3-phenylpropanoyl)aminopropylphosphinic acid (255 mg) obtained in (a) of Example 2 was added with hexamethyldisilazane (0.3 ml), and the mixture was stirred at 110° C. for 30 minutes. The mixture was then added with the ethyl 2-(4-benzyloxycarbonylaminobutyl)acrylate (356 mg) obtained in the above step (e), and further stirred at the same temperature for 18 hours. The organic substances were extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and then the residue was purified by Sephadex LH-20 (300 cc, methylene chloride:methanol=1:1) to obtain crude ethyl 6-benzyloxycarbonylamino-2-((2-methyl-1-(3-phenylpropanoylamino)propyl)hydroxyphosphinoyl)methylhexanoate (222 mg, 41%). This compound was used in the following reaction without further purification. (g) The crude ethyl 6-benzyloxycarbonylamino-2-((2-methyl-1-(3-phenylpropanoylamino)propyl)hydroxyphosphinoyl)methylhexanoate (222 mg) obtained in the above step (f) was dissolved in a mixed solvent of ethanol:water (10:7) (3.4 ml). The mixture was added with 1 N aqueous sodium hydroxide (0.6 ml) and stirred at room temperature for 3 hours, at 50° C. for 2 hours, and then at room temperature for 16 hours. The reaction mixture was acidified with hydrochloric acid and the organic substances were extracted with ethyl acetate, and then the extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The residue was concentrated to obtain crude 6-benzyloxycarbonylamino-2-((2-methyl-1-(3-phenylpropanoylamino)propyl)hydroxyphosphinoyl)methylhexanoic acid (181 mg, 86%). This compound was subjected to the measurement of molecular weight and then used in the following reaction without further purification.

Workup

  1. customobtained in the above step (e)
  2. stirringfurther stirred at the same temperature for 18 hours
  3. extractionThe organic substances were extracted with ethyl acetate
  4. washthe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe residue was purified by Sephadex

Sources & evidence

ORD record
ord-e184e70b4ea94494a225c06badf62bd6
Source dataset
uspto-grants-2003_06
Patent number
US06576627B1

Reaction notes

Loading…