2-(Trimethylsilyl)ethyl chloroformate → HCID 178504278, compound

HRID 2291528Notes

Reaction equation

HRID 2291528 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[N:8]=[CH:7][NH:6][CH:5]=1.[CH3:9][Si:10]([CH3:18])([CH3:17])[CH2:11][CH2:12][O:13][C:14](Cl)=[O:15]>CCOCC>[CH3:9][Si:10]([CH3:18])([CH3:17])[CH2:11][CH2:12][O:13][C:14]([NH:1][CH2:2][CH2:3][C:4]1[N:8]=[CH:7][NH:6][CH:5]=1)=[O:15]

Participants

4

Reactant 2

HCID 109101682-(Trimethylsilyl)ethyl chloroformateHCID 178419017HCID 178419017, compound

Product 1

HCID 178504278HCID 178504278, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

1.84 g (10 mmol) of histamine dihydrochloride is slurried in 50 ml of methylene chloride, and 6.2 ml (44 mmol) of triethylamine is added. The thus resultant mixture is added portionwise to 2-trimethylsilylethylchloroformate in toluene (prepared as described above) at 10°-15° C. The reaction mixture is stirred at room temperature overnight. Undissolved material is filtered off and identified by NMR as being triethylamine hydrochloride. The toluene solution is evaporated, the residue then being slurried in 30 ml of ethyl acetate. 1.0 g of undissolved triethylamine hydrochloride is removed by filtration. The ethyl acetate solution is evaporated, and the residue is slurried twice in petroleum ether. The petroleum ether solutions are evaporated and 1.0 g of a semicrystalline product is obtained; by NMR analysis this product is identified as being histamine in which both the amino group and ring nitrogen have been acylated with 2-trimethylsilylethylchloroformate. The acyl group on the ring nitrogen is removed by treatment of the product for 2 hours with 100 μl of triethylamine in 50 ml of methanol. The solution is evaporated to leave an oil which is transformed into white crystals by treatment with 30 ml of ether. More precipitate is obtained upon addition of 75 ml petroleum ether. 560 mg of I is obtained upon filtration. The structure of the product is established with the aid of its NMR spectrum. 1H NMR spectrum (CDCl3) expressed as values: 2H 7.60 s, 5H 6.82 s, --NH-- 5.20, --CH2CH2 --O-- 4.15 t, --OCONHCH2 -- 3.50 m, 4-CH2 -imidazole 2.82 t, SiCH2CH2 1.00 t, (CH3)3Si 0.03 s.

Workup

  1. customThe acyl group on the ring nitrogen is removed by treatment of the product for 2 hours with 100 μl of triethylamine in 50 ml of methanol
  2. customThe solution is evaporated
  3. customto leave an oil which
  4. custom560 mg of I is obtained upon filtration
  5. custom2H 7.60 s, 5H 6.82 s

Sources & evidence

ORD record
ord-afab06b415134fe5a1e9d3d6c3dd7431
Source dataset
uspto-grants-1989_01
Patent number
US04797370

Reaction notes

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