tert-butyl N-(2-amino-2-sulfanylideneethyl)carbamate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2S, 4R)-2-bromoacetyl-4-methanesulfonyloxy-1- (4-nitrobenzyloxycarbonyl)pyrrolidine (20 g) in a mixture of methanol (200 ml) and dichloromethane (200 ml) was added 2-(N-t-butoxycarbonylamino)thioacetamide (20 g) at room temperature. After stirring at ambient temperature for 12 hours, the mixture was poured into ethyl acetate, washed with saturated sodium bicarbonate and brine successively. The dried organic layer was evaporated, and the obtained oil was subjected to a column chromatography on silica gel and eluted with a mixture of acetone and dichloromethane (1:5, V/V) to give (2S,4R)-2-[2-(N-t-butoxycarbonylamino) methylthiazol-4-yl]-4-methanesulfonyloxy-1- (4-nitrobenzyloxycarbonyl)pyrrolidine (9.7 g). washed with saturated sodium bicarbonate and brine successively The dried organic layer was evaporated eluted with a mixture of acetone and dichloromethane (1:5, V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2S,4R)-2-bromoacetyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (20 g) in a mixture of methanol (200 ml) and dichloromethane (200 ml) was added 2-(N-t-butoxycarbonylamino)thioacetamide (20 g) at room temperature. After stirring at ambient temperature for 12 hours, the mixture was poured into ethyl acetate, washed with saturated sodium bicarbonate and brine successively. The dried organic layer was evaporated, and the obtained oil was subjected to a column chromatography on silica gel and eluted with a mixture of acetone and dichloromethane (1:5, V/V) to give (2S,4R)-2-[2-(N-t-butoxycarbonylamino)methylthiazol-4-yl]-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (9.7 g). washed with saturated sodium bicarbonate and brine successively The dried organic layer was evaporated eluted with a mixture of acetone and dichloromethane (1:5, V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2S, 4R)-2-bromoacetyl-4-methanesulfonyloxy-1- (4-nitrobenzyloxycarbonyl)pyrrolidine (20 g) in a mixture of methanol (200 ml) and dichloromethane (200 ml) was added 2-(N-t-butoxycarbonylamino)thioacetamide (20 g) at room temperature. After stirring at ambient temperature for 12 hours, the mixture was poured into ethyl acetate, washed with saturated sodium bicarbonate and brine successively. The dried organic layer was evaporated, and the obtained oil was subjected to a column chromatography on silica gel and eluted with a mixture of acetone and dichloromethane (1:5, V/V) to give (2S,4R)-2-[2-(N-t-butoxycarbonylamino) methylthiazol-4-yl]-4-methanesulfonyloxy-1- (4-nitrobenzyloxycarbonyl)pyrrolidine (9.7 g). washed with saturated sodium bicarbonate and brine successively The dried organic layer was evaporated eluted with a mixture of acetone and dichloromethane (1:5, V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2S, 4R)-2-bromoacetyl-4-methanesulfonyloxy-1- (4-nitrobenzyloxycarbonyl)pyrrolidine (20 g) in a mixture of methanol (200 ml) and dichloromethane (200 ml) was added 2-(N-t-butoxycarbonylamino)thioacetamide (20 g) at room temperature. After stirring at ambient temperature for 12 hours, the mixture was poured into ethyl acetate, washed with saturated sodium bicarbonate and brine successively. The dried organic layer was evaporated, and the obtained oil was subjected to a column chromatography on silica gel and eluted with a mixture of acetone and dichloromethane (1:5, V/V) to give (2S,4R)-2-[2-(N-t-butoxycarbonylamino) methylthiazol-4-yl]-4-methanesulfonyloxy-1- (4-nitrobenzyloxycarbonyl)pyrrolidine (9.7 g). washed with saturated sodium bicarbonate and brine successively The dried organic layer was evaporated eluted with a mixture of acetone and dichloromethane (1:5, V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2S,4R)-2-bromoacetyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (20 g) in a mixture of methanol (200 ml) and dichloromethane (200 ml) was added 2-(N-t-butoxycarbonylamino)thioacetamide (20 g) at room temperature. After stirring at ambient temperature for 12 hours, the mixture was poured into ethyl acetate, washed with saturated sodium bicarbonate and brine successively. The dried organic layer was evaporated, and the obtained oil was subjected to a column chromatography on silica gel and eluted with a mixture of acetone and dichloromethane (1:5, V/V) to give (2S,4R)-2-[2-(N-t-butoxycarbonylamino)methylthiazol-4-yl]-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (9.7 g). washed with saturated sodium bicarbonate and brine successively The dried organic layer was evaporated eluted with a mixture of acetone and dichloromethane (1:5, V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The same procedure as in Preparation 10 was repeated except that 1.9 g of (N-t-butoxycarbonylamino) acetothioamide and 2.49 g of 2'-bromoacetophenone were used, thereby obtaining 1.32 g of the title compound. The same procedure as in Preparation 10

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5.02 g of (tert-butoxycarbonylamino)acetothioamide in 75 ml of ethanol were added 3.92 ml of ethyl 2-chloroacetoacetate and 2.75 g of calcium carbonate, and the mixture was stirred at 50° C. for 6 hours. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with a 5:1 mixture of toluene and ethyl acetate to give 5.65 g (yield 71%) of the title compound. The reaction solution was filtered the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography eluting with a 5:1 mixture of toluene and ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 10 g of the above-obtained (tert-butoxycarbonylamino)acetothioamide in 150 ml of ethanol were added 7.3 ml of ethyl bromopyruvate and 2.7 g of calcium carbonate, and the mixture was stirred at room temperature for 6 hours. The reaction solution was filtered, and the filtrate was concentrated to dryness under reduced pressure. The residue was dissolved in chloroform. The solution was washed with a saturated aqueous solution of sodium hydrogencarbonate and a small amount of water, and then dried over anhydrous magnesium sulfate. The resultant was concentrated under reduced pressure, and isopropyl ether was added to the residue. The crystals precipitated were collected by filtration, and dried under reduced pressure to give 11.2 g (yield 74%) of ethyl 2-(tert-butoxycarbonylamino)methylthiazole-4-carboxylate. The reaction solution was filtered the filtrate was concentrated to dryness under reduced pressure The residue was dissolved in chloroform The solution was washed with a saturated aqueous solution of sodium hydrogencarbonate a small amount of water, and then dried over anhydrous magnesium sulfate The resultant was concentrated under reduced pressure, and isopropyl ether was added to the residue The crystals precipitated were collected by filtration dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25 g of ammonia gas and 50 g of hydrogen sulfide gas were successively dissolved in 230 ml of methanol with ice-cooling and stirring. To this was added 71.45 g of (tert-butoxycarbonylamino)acetonitrile, and the mixture was stirred overnight at room temperature. The reaction solution was cooled with ice. To this was slowly added 500 ml of water, and the mixture was stirred for an additional 2 hours with ice- cooling. The crystals precipitated were collected by filtration, washed with 300 ml of cold water, and then dried under reduced pressure to give 65.88 g of (tert-butoxycarbonyl-amino)acetothioamide as colorless crystals. cooling the mixture was stirred overnight at room temperature The reaction solution was cooled with ice the mixture was stirred for an additional 2 hours with ice- cooling The crystals precipitated were collected by filtration washed with 300 ml of cold water dried under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2S,4R)-2-bromoacetyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (20 g) in a mixture of methanol (200 ml) and dichloromethane (200 ml) was added 2-(N-t-butoxycarbonylamino)thioacetamide (20 g) at room temperature. After stirring at ambient temperature for 12 hours, the mixture was poured into ethyl acetate, washed with saturated sodium bicarbonate and brine successively. The dried organic layer was evaporated, and the obtained oil was subjected to a column chromatography on silica gel and eluted with a mixture of acetone and dichloromethane (1:5, V/V) to give (2S,4R)-2-[2-(N-t-butoxycarbonylamino)methylthiazol-4-yl]-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (9.7 g). washed with saturated sodium bicarbonate and brine successively The dried organic layer was evaporated eluted with a mixture of acetone and dichloromethane (1:5, V/V)