Triethylamine → N-methyl[[(2-methylpropyl)(2-thioxo-1,3,2-benzodioxaphosphol-2-yl)amino]thio]carbamic fluoride

HRID 223442Notes

Reaction equation

HRID 223442 reaction equation
[CH3:1][CH:2]([CH3:15])[CH2:3][NH:4][P:5]1(=[S:14])[O:9][C:8]2[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=2[O:6]1.C(N(CC)CC)C.[S:23](Cl)Cl.[CH3:26][NH:27][C:28]([F:30])=[O:29]>O1CCCC1.CCOCC.CN(C)C=O>[CH3:26][N:27]([S:23][N:4]([CH2:3][CH:2]([CH3:15])[CH3:1])[P:5]1(=[S:14])[O:9][C:8]2[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=2[O:6]1)[C:28]([F:30])=[O:29]

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 25353Sulfur dichlorideHCID 12545956Methylcarbamyl fluorideHCID 20475425N-(2-methylpropyl)-2-thioxo-1,3,2-benzodioxaphosphol-2-amine

Product 1

HCID 53825165N-methyl[[(2-methylpropyl)(2-thioxo-1,3,2-benzodioxaphosphol-2-yl)amino]thio]carbamic fluoride

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of N-(2-methylpropyl)-2-thioxo-1,3,2-benzodioxaphosphol-2-amine (16.2 g, 66.6 mmol) and triethylamine (7.3 g, 72 mmol) in tetrahydrofuran (50 ml) is added dropwise over 10 minutes to a solution of sulfur dichloride (8.1 g, 78.7 mmol) in tetrahydrofuran (50 ml) with cooling to maintain a temperature of -5° to 0°. After the addition, the mixture is stirred for two hours then diluted with ether (100 ml). The reaction mixture is filtered under nitrogen and the filtrate concentrated in vacuo. The residue is dissolved in dimethyl formamide (50 ml) and N-methyl carbamoyl fluoride (5.8 g, 75.3 mmol) added at once followed by dropwise addition of triethylamine (7.3 g, 72 mmol) in dimethyl formamide (10 ml) over 10 minutes with cooling in a bath at -25°. After the addition the mixture is stirred for two hours in a bath at 0°. The mixture is diluted with ether, washed with ice cold water, dried and concentrated to leave a crude N-methyl[[(2-methylpropyl)(2-thioxo-1,3,2-benzodioxaphosphol-2-yl)amino]thio]carbamic fluoride II'''. The carbamic fluoride is dissolved in methylene chloride (50 ml) and a solution of methyl N-hydroxyethanimidothioate (7.00 g, 66.6 mmol), tetraethylammonium chloride (1.00 g, 6.04 mmol) and sodium hydroxide (2.20 g, 80 mmol) in water (50 ml) is added at once. The mixture is stirred for 20 hours at room temperature, the phases separated, and the organic phase washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residual oil is triturated with ether to precipitate the product methyl N-[[[methyl[[(2-methypropyl)(2-thioxo-1,3,2-benzodioxaphosphol-2-yl)amino]thio]carbonyl]oxy]ethanimidothioate (I''')

Workup

  1. temperaturewith cooling
  2. temperatureto maintain a temperature of -5° to 0°
  3. additionAfter the addition
  4. filtrationThe reaction mixture is filtered under nitrogen
  5. concentrationthe filtrate concentrated in vacuo
  6. dissolutionThe residue is dissolved in dimethyl formamide (50 ml)
  7. temperaturewith cooling in a bath at -25°
  8. additionAfter the addition the mixture
  9. stirringis stirred for two hours in a bath at 0°
  10. washwashed with ice cold water
  11. customdried
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-46be6d613a724cd2a667b314158d340b
Source dataset
uspto-grants-1982_10
Patent number
US04354975

Reaction notes

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