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

Temperature

-25 °C

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° C. 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, 66.5 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-methylpropyl)(2-thioxo-1,3,2-benzodioxaphosphol-2-yl)amino]thio]amino]carbonyl]oxy]ethanimidothioate I"'.

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. additionAfter the addition the mixture
8. stirringis stirred for two hours in a bath at 0°
9. washwashed with ice cold water
10. customdried
11. concentrationconcentrated

ORD record

ord-73306d2f07364eb581b9198dcf5a255f

Source dataset

uspto-grants-1984_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04424368