Sodium Hydroxide → alpha-[[2-[[Bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]thio]-4-carboxytoluene

HRID 417807Notes

Reaction equation

HRID 417807 reaction equation
Br[CH2:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9]C)=[O:8])=[CH:5][CH:4]=1.NC(N)=[S:15].[OH-].[Na+].[Cl:19][CH2:20][CH2:21][N:22]([CH2:46][CH2:47][Cl:48])[P:23]([N:39]([CH2:43][CH2:44][Cl:45])[CH2:40][CH2:41][Cl:42])(=[O:38])[O:24][CH2:25][CH2:26]OS(C1C=CC(Br)=CC=1)(=O)=O>C(O)C.CO>[Cl:19][CH2:20][CH2:21][N:22]([P:23]([N:39]([CH2:43][CH2:44][Cl:45])[CH2:40][CH2:41][Cl:42])([O:24][CH2:25][CH2:26][S:15][CH2:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1)=[O:38])[CH2:46][CH2:47][Cl:48]

Participants

7

Reactant 4

HCID 14798Sodium Hydroxide2×HCID 256687Methyl 4-(bromomethyl)benzoateHCID 2723790ThioureaHCID 179493772-(4-Bromobenzene-sulfonyloxy)ethyl tetrakis(2-chloroethyl)phosphorodiamidate

Product 1

HCID 66650850alpha-[[2-[[Bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]thio]-4-carboxytoluene

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent2×

Procedure

4-(Thiomethyl)benzoic acid was prepared from methyl 4-(bromomethyl)benzoate using the procedure of Org. Syn. Coll. Vol. 3, page 363 (reaction with thiourea in ethanol, followed by hydrolysis of the ester with aqueous sodium hydroxide). 4-(Thiomethyl)benzoic acid, 2 g, was alkylated with 2-(4-bromobenzenesulfonyloxy)ethyl tetrakis(2-chloroethyl)phosphorodiamidate, 15.8 mL of 0.83 M, in 10 mL methanol and 6.25 mL of 4 M sodium hydroxide in methanol. The resulting product after filtration and concentration was a pale yellow oil, which was dissolved in saturated aqueous sodium bicarbonate and washed twice with 100 mL isopropyl acetate. The aqueous extracts were combined, acidified to pH ˜1 with sulfuric acid, and back extracted twice with into 100 mL isopropyl acetate. The isopropyl acetate layers were combined, dried over MgSO4, filtered, and concentrated under vacuum to give α-[[2-[[bis[bis(2-chloroethyl)amino]phosphinyl]oxy]ethyl]thio]-4-carboxytoluene as a pale yellow oil, 5.4 g, with product identity verified by LC-MS.

Workup

  1. filtrationThe resulting product after filtration and concentration
  2. dissolutionwas dissolved in saturated aqueous sodium bicarbonate
  3. washwashed twice with 100 mL isopropyl acetate
  4. extractionback extracted twice with into 100 mL isopropyl acetate
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-009bf3a542894e128f69607752be9a29
Source dataset
uspto-grants-2012_01
Patent number
US08093231B2

Reaction notes

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