Hydrochloric Acid → HCID 11670915, compound

HRID 417804Notes

Reaction equation

HRID 417804 reaction equation
[Cl:1][CH2:2][CH2:3][N:4]([P:8]([N:29]([CH2:33][CH2:34][Cl:35])[CH2:30][CH2:31][Cl:32])([O:10][CH2:11][CH2:12][S:13]([CH2:16][C@@H:17]([C:26]([OH:28])=[O:27])[NH:18]C(OC(C)(C)C)=O)(=[O:15])=[O:14])=[O:9])[CH2:5][CH2:6][Cl:7].Cl.C(OCC)C>C(OCC)(=O)C>[Cl:32][CH2:31][CH2:30][N:29]([P:8]([N:4]([CH2:3][CH2:2][Cl:1])[CH2:5][CH2:6][Cl:7])([O:10][CH2:11][CH2:12][S:13]([CH2:16][C@@H:17]([C:26]([OH:28])=[O:27])[NH2:18])(=[O:14])=[O:15])=[O:9])[CH2:33][CH2:34][Cl:35]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3283Diethyl EtherHCID 86601851HCID 86601851, compound

Product 1

HCID 11670915HCID 11670915, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

3-[[2-[[Bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]sulfonyl]-N-tert-butoxycarbonyl-L-alanine, 1.82 g (2.91 mmol), was dissolved in 18 mL ethyl acetate, and to this solution was added hydrogen chloride, 1.75 mL of 2 M solution in diethyl ether (3.5 mmol); and the resulting mixture stirred under nitrogen overnight at room temperature. HPLC analysis of the reaction mixture showed that the reaction was incomplete (20.8% product), so an additional 0.9 equivalents of hydrogen chloride solution was added and the reaction mixture stirred for an additional 4 days, resulting in the formation of a slurry. HPLC analysis of the reaction mixture showed 99.7% product and 0.3% starting material. The slurry was filtered under nitrogen, washed with ethyl acetate, and dried under nitrogen for 3 hours to give 3-[[2-[[bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]sulfonyl]-L-alanine, compound 70A, as the hydrochloride salt, off-white solid, 0.90 g (55% yield). HPLC analysis of the product showed a purity of 99.7%. 1H NMR: δ 8.50-9.10 (bs, 3H), 4.43 (m, 1H), 4.32 (m, 2H), 3.93-3.97 (m, 1H), 3.70-3.80 (m, 11H), 3.34 (m, 8H). 13C NMR: δ 168.2, 58.0, 57.9, 53.8, 53.7, 53.0, 48.3, 48.3, 47.1, 42.3. 31P NMR: δ 17.5 (s, 1P). Mass spectrum: m/z 526 [C13H26Cl4N3O6PS+H]+.

Workup

  1. stirringthe reaction mixture stirred for an additional 4 days
  2. customresulting in the formation of a slurry
  3. filtrationThe slurry was filtered under nitrogen
  4. washwashed with ethyl acetate
  5. customdried under nitrogen for 3 hours

Sources & evidence

ORD record
ord-21f85075244548c290f2d799eaf3bc60
Source dataset
uspto-grants-2012_01
Patent number
US08093231B2

Reaction notes

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