2,2-dichloroacetonitrile

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

Procedure: Dichloroacetonitrile (33.67 mL, 420 mmol) was added slowly, whilst maintaining the temperature below 0° C., over 30 min. to a solution of sodium methoxide ((25% w/w) 9.63 mL, 43 mmol) in methanol (84.5 mL) which was precooled to −10° C. This was allowd to stir for 30 min. before the addition of L-cysteine ethyl ester hydrochloride (78.32 g, 422 mmol) dissolved in methanol (67.4 mL) and then stirred overnight at RT. Water (136 mL) followed by DCM (136 mL) was added to the mixture and stirred vigorously. The organic layer was separated and the aqueous layer was reextracted with a further 136 mL of DCM. This was concentrated in vacuo to give the crude product (94.1 g, 93%). whilst maintaining the temperature below 0° C. was added to the mixture stirred vigorously The organic layer was separated This was concentrated in vacuo

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

Procedure: A solution of dichloroacetonitrile (215 g, 1.96 mol) in methanol (200 mL) was added drop-wise to a −5° C. solution of sodium methoxide (15.4 g, 0.285 mol) in methanol (500 mL). A solution of ethyl serinate, hydrochloride salt (382 g, 2.45 mol) in methanol (300 mL) was then added to the −5° C. reaction mixture, which was subsequently allowed to stir at room temperature for 16 hours. Dichloromethane (1 L) and water (800 mL) were added, and the aqueous layer was extracted with dichloromethane (1 L); the combined organic layers were concentrated in vacuo to provide the product as a yellow oil, which was used in the next step without additional purification. Yield: 300 g, 1.4 mol, 71%. 1H NMR (400 MHz, CDCl3) δ 6.29 (s, 1H), 4.90 (dd, J=10.8, 8.3 Hz, 1H), 4.74 (dd, J=8.8, 8.3 Hz, 1H), 4.66 (dd, J=10.8, 8.9 Hz, 1H), 3.82 (s, 3H). the aqueous layer was extracted with dichloromethane (1 L) the combined organic layers were concentrated in vacuo

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

Procedure: A solution of dichloroacetonitrile (215 g, 1.96 mol) in methanol (200 mL) was added drop-wise to a −5° C. solution of sodium methoxide (15.4 g, 0.285 mol) in methanol (500 mL). A solution of ethyl serinate, hydrochloride salt (382 g, 2.45 mol) in methanol (300 mL) was then added to the −5° C. reaction mixture, which was subsequently allowed to stir at room temperature for 16 hours. Dichloromethane (1 L) and water (800 mL) were added, and the aqueous layer was extracted with dichloromethane (1 L); the combined organic layers were concentrated in vacuo to provide the product as a yellow oil, which was used in the next step without additional purification. Yield: 300 g, 1.4 mol, 71%. 1H NMR (400 MHz, CDCl3) δ 6.29 (s, 1H), 4.90 (dd, J=10.8, 8.3 Hz, 1H), 4.74 (dd, J=8.8, 8.3 Hz, 1H), 4.66 (dd, J=10.8, 8.9 Hz, 1H), 3.82 (s, 3H). the aqueous layer was extracted with dichloromethane (1 L) the combined organic layers were concentrated in vacuo

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

Procedure: A solution of dichloroacetonitrile (215 g, 1.96 mol) in methanol (200 mL) was added drop-wise to a −5° C. solution of sodium methoxide (15.4 g, 0.285 mol) in methanol (500 mL). A solution of ethyl serinate, hydrochloride salt (382 g, 2.45 mol) in methanol (300 mL) was then added to the −5° C. reaction mixture, which was subsequently allowed to stir at room temperature for 16 hours. Dichloromethane (1 L) and water (800 mL) were added, and the aqueous layer was extracted with dichloromethane (1 L); the combined organic layers were concentrated in vacuo to provide the product as a yellow oil, which was used in the next step without additional purification. Yield: 300 g, 1.4 mol, 71%. 1H NMR (400 MHz, CDCl3) 6.29 (s, 1H), 4.90 (dd, J=10.8, 8.3 Hz, 1H), 4.74 (dd, J=8.8, 8.3 Hz, 1H), 4.66 (dd, J=10.8, 8.9 Hz, 1H), 3.82 (s, 3H). the aqueous layer was extracted with dichloromethane (1 L) the combined organic layers were concentrated in vacuo

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

Procedure: Dichloroacetonitrile (33.67 mL, 420 mmol) was added slowly, whilst maintaining the temperature below 0° C., over 30 min. to a solution of sodium methoxide ((25% w/w) 9.63 mL, 43 mmol) in methanol (84.5 mL) which was precooled to −10° C. This was allowd to stir for 30 min. before the addition of L-cysteine ethyl ester hydrochloride (78.32 g, 422 mmol) dissolved in methanol (67.4 mL) and then stirred overnight at RT. Water (136 mL) followed by DCM (136 mL) was added to the mixture and stirred vigorously. The organic layer was separated and the aqueous layer was reextracted with a further 136 mL of DCM. This was concentrated in vacuo to give the crude product (94.1 g, 93%). whilst maintaining the temperature below 0° C. was added to the mixture stirred vigorously The organic layer was separated This was concentrated in vacuo

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

Procedure: A solution of dichloroacetonitrile (215 g, 1.96 mol) in methanol (200 mL) was added drop-wise to a −5° C. solution of sodium methoxide (15.4 g, 0.285 mol) in methanol (500 mL). A solution of ethyl serinate, hydrochloride salt (382 g, 2.45 mol) in methanol (300 mL) was then added to the −5° C. reaction mixture, which was subsequently allowed to stir at room temperature for 16 hours. Dichloromethane (1 L) and water (800 mL) were added, and the aqueous layer was extracted with dichloromethane (1 L); the combined organic layers were concentrated in vacuo to provide the product as a yellow oil, which was used in the next step without additional purification. Yield: 300 g, 1.4 mol, 71%. 1H NMR (400 MHz, CDCl3) δ 6.29 (s, 1H), 4.90 (dd, J=10.8, 8.3 Hz, 1H), 4.74 (dd, J=8.8, 8.3 Hz, 1H), 4.66 (dd, J=10.8, 8.9 Hz, 1H), 3.82 (s, 3H). the aqueous layer was extracted with dichloromethane (1 L) the combined organic layers were concentrated in vacuo