Nitrogen mustard hydrochloride → HCID 19084705, compound

HRID 962484Notes

Reaction equation

HRID 962484 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:15][N:16]([CH2:20][CH2:21]Cl)[CH2:17][CH2:18]Cl.Cl>CS(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:9]([O:11][CH3:12])=[O:10])[CH2:21][CH2:20][N:16]([CH3:15])[CH2:17][CH2:18]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 5935Nitrogen mustard hydrochlorideHCID 24758Sodium hydrideHCID 2733233Methyl 2-(4-fluorophenyl)acetate

Product 1

HCID 19084705HCID 19084705, compoundYield 30.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Methyl 4-fluorophenylacetate (24.4 g) was dissolved in dry dimethyl sulphoxide (150 ml) and added dropwise to sodium hydride (15.7 g of an 80% dispersion in oil) under nitrogen. After 20 minutes mechlorethamine hydrochloride (24 g) in dry dimethyl sulphoxide (125 ml) was added over a period of 20 minutes. The reaction was poured onto ice (200 ml) and left overnight. The mixture was extracted with diethyl ether (50×250 ml) and the combined organic solutions were extracted with 5N HCl (100 ml). The aqueous solution was treated with potassium carbonate and extracted with ethyl acetate (3×250 ml). The combined organic extracts were dried (MgSO4) and concentrated in vacuo to afford a brown oil. The oil was purified by flash chromatography eluting with ethyl acetate graduated to 8% methanol in ethyl acetate, to afford the title compound (9.5 g). 1H NMR (360 MHz, CDCl3) δ 1.9-2.03 (2H, m), 2.07-2.19 (2H, m), 2.27 (3H, s), 2.51-2.62 (2H, m), 2.72-2.86 (2H, m), 3.65 (3H, s), 6.98-7.06 (2H, m), 7.27-7.39 (2H, m). MS (Cl+) 224 [M+H]+.

Workup

  1. additionThe reaction was poured onto ice (200 ml)
  2. extractionThe mixture was extracted with diethyl ether (50×250 ml)
  3. extractionthe combined organic solutions were extracted with 5N HCl (100 ml)
  4. additionThe aqueous solution was treated with potassium carbonate
  5. extractionextracted with ethyl acetate (3×250 ml)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto afford a brown oil
  9. customThe oil was purified by flash chromatography
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-d150322b85664e9892cfa3911de7f2d8
Source dataset
uspto-grants-1998_06
Patent number
US05760018

Reaction notes

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