Trifluoroacetic acid → HCID 86620330, compound

HRID 1441906Notes

Reaction equation

HRID 1441906 reaction equation
[Cl:1]CCN(CCCl)P(N(CCCl)CCCl)(=O)OCCSCCN(C(C)C)C(C)C.FC(F)(F)C(O)=O.C(OO)(=O)C.[Cl:42][CH2:43][CH2:44][N:45]([CH2:70][CH2:71][Cl:72])[P:46]([N:63]([CH2:67][CH2:68][Cl:69])[CH2:64][CH2:65][Cl:66])(=[O:62])[O:47][CH2:48][CH2:49][S:50]([CH2:53][CH2:54][N:55]([CH:59]([CH3:61])[CH3:60])[CH:56]([CH3:58])[CH3:57])(=[O:52])=[O:51]>CN(C)C=O.C(O)(=O)C.C(OCC)(=O)C>[ClH:1].[Cl:66][CH2:65][CH2:64][N:63]([CH2:67][CH2:68][Cl:69])[P:46]([N:45]([CH2:44][CH2:43][Cl:42])[CH2:70][CH2:71][Cl:72])(=[O:62])[O:47][CH2:48][CH2:49][S:50]([CH2:53][CH2:54][N:55]([CH:59]([CH3:60])[CH3:61])[CH:56]([CH3:58])[CH3:57])(=[O:52])=[O:51]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 6585Peracetic AcidHCID 25025067HCID 25025067, compoundHCID 86620331HCID 86620331, compound2×

Product 1

HCID 86620330HCID 86620330, compoundYield 100%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-{[2-(diisopropylamino)ethyl]thio}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate (2.3 g, 4.3 mmol) in dimethylformamide (30 mL) at 0° C. was treated with trifluoroacetic acid (1.6 mL, 21.5 mmol, 5.0 eq.) and stirred at 0° C. for an additional 10 minutes. Peracetic acid (726 μL of a 32%/wt solution in acetic acid, 10.8 mmol, 2.5 eq.) was added over 5 minutes, then the mixture was allowed to warm to room temperature. Stirring was continued until analysis of an aliquot by LC/MS indicated complete conversion of 2-{[2-(diisopropylamino)ethyl]thio}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate to 2-{[2-(diisopropylamino)ethyl]sulfonyl}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate (typically about 2 hours). The reaction mixture was diluted with ethyl acetate (800 mL) and washed with a 1:1 mixture of 0.2M aqueous Na2S2O4 and saturated aqueous NaHCO3 (2×800 mL). The organic layer was separated, dried over anhydrous MgSO4, filtered, and treated with excess hydrochloric acid (4.0M in dioxane). The resulting hazy solution was concentrated under vacuum to give 2-{[2-(diisopropylamino)ethyl]sulfonyl}ethyl N,N,N′,N′-tetrakis(2-chloroethyl)-phosphorodiamidate hydrochloride as a clear oil (2.53 g, 100% yield). MS (ES+): m/z=564 [C18H39Cl4N3O4PS+H]; 1H NMR (CD3OD): δ=1.44 (t, J=6.3 Hz, 12H), 3.41-3.52 (m, 8H), 3.64-3.87 (m, 16H), 4.53 (q, J=5.5 Hz, 2H); 31P NMR (CD3OD): δ=18.01.

Workup

  1. temperatureto warm to room temperature
  2. stirringStirring
  3. customtypically about 2 hours
  4. washwashed with a 1:1 mixture of 0.2M aqueous Na2S2O4 and saturated aqueous NaHCO3 (2×800 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. additiontreated with excess hydrochloric acid (4.0M in dioxane)
  9. concentrationThe resulting hazy solution was concentrated under vacuum

Sources & evidence

ORD record
ord-b532b0171ddf4c5db8def9bbe715d34e
Source dataset
uspto-grants-2010_02
Patent number
US07655799B2

Reaction notes

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