trifluoromethyl hypofluorite

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A well-stirred solution of 3β, 17β-di(trifluoroacetoxy)-5α-androstane (2.5 g, 5.15 mmole, prepared by treatment of 5α-androstane-3β,17β-diol with trifluoroacetic anhydride in pyridine), nitrobenzene (800 mg, 6.5 mmole) and sodium trifluoroacetate (10 g, 73.5 mmole) in fluorotrichloromethane (45 ml) was treated with trifluoromethyl hypofluorite (8.5 mmole) at -20° for 2.5 hours, air being admitted to the reaction vessel during this time. Thereafter the solution was purged with nitrogen and the solvent was removed in vacuo. The residue was dissolved in chloroform and the resulting solution was washed with aqueous sodium bicarbonate and water and was then dried, whereafter the product was chromatographed on silica gel (125 g). Elution with chloroform:hexane (3:7) gave unreacted starting material (308 mg), while subsequent elution with chloroform:hexane (7:13) gave 3β,17β-di(trifluoroacetoxy)-9α-fluoro-5α-androstane (1.02 g), which crystallized from hexane as prisms (917 mg) m.p. 140°-142°; [α] 24D - 22° (c 1.47, CHCl3). (Found C,55.10; H,5.78; F,26.35%;m/e 502. C33H29O4F7 requires C,54.97; H,5.82; F,26.47%; M+ 502). Thereafter the solution was purged with nitrogen the solvent was removed in vacuo The residue was dissolved in chloroform the resulting solution was washed with aqueous sodium bicarbonate and water was then dried, whereafter the product was chromatographed on silica gel (125 g) Elution with chloroform:hexane (3:7) gave unreacted while subsequent elution with chloroform:hexane (7:13)

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

Procedure: A well-stirred solution of 3β, 17β-di(trifluoroacetoxy)-5α-androstane (2.5 g, 5.15 mmole, prepared by treatment of 5α-androstane-3β,17β-diol with trifluoroacetic anhydride in pyridine), nitrobenzene (800 mg, 6.5 mmole) and sodium trifluoroacetate (10 g, 73.5 mmole) in fluorotrichloromethane (45 ml) was treated with trifluoromethyl hypofluorite (8.5 mmole) at -20° for 2.5 hours, air being admitted to the reaction vessel during this time. Thereafter the solution was purged with nitrogen and the solvent was removed in vacuo. The residue was dissolved in chloroform and the resulting solution was washed with aqueous sodium bicarbonate and water and was then dried, whereafter the product was chromatographed on silica gel (125 g). Elution with chloroform:hexane (3:7) gave unreacted starting material (308 mg), while subsequent elution with chloroform:hexane (7:13) gave 3β,17β-di(trifluoroacetoxy)-9α-fluoro-5α-androstane (1.02 g), which crystallized from hexane as prisms (917 mg) m.p. 140°-142°; [α] 24D - 22° (c 1.47, CHCl3). (Found C,55.10; H,5.78; F,26.35%;m/e 502. C33H29O4F7 requires C,54.97; H,5.82; F,26.47%; M+ 502). Thereafter the solution was purged with nitrogen the solvent was removed in vacuo The residue was dissolved in chloroform the resulting solution was washed with aqueous sodium bicarbonate and water was then dried, whereafter the product was chromatographed on silica gel (125 g) Elution with chloroform:hexane (3:7) gave unreacted while subsequent elution with chloroform:hexane (7:13)

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

Procedure: A solution of 1-trifluoroacetoxyadamantane (1.0 g, 4.0 mmole, prepared by reacting adamantan-1-ol with trifluoroacetic anhydride in dry pyridine) in fluorotrichloromethane (10 ml), containing m-dinitrobenzene (80 mg, 0.48 mmole), was treated with trifluoromethyl hypofluorite (4.5 mmole) at -25° for 24 hours, air being recrystallization admitted to the reaction vessel during this time. The product was recovered in a similar manner to that described in Example 3 and was chromatographed on silica (100 g). Elution with chloroform:hexane (1:5) afforded unreacted starting material (152 mg), while elution with chloroform:hexane (1:4) gave liquid 3-fluoro-1-trifluoroacetoxyadamantane (489 mg) which appeared homogeneous by g.l.c. This product sublimed at 70° (bath)/1 mm Hg to give a crystalline solid m.p. 28°-32°; νmax (film) 1780 cm-1 ; PMR 1.5-2.6 (m, adamantyl protons); FMR φ* + 76.2 (s, CF3COO--) and + 133.5 (broad s) ppm. air being recrystallization The product was recovered in a similar manner to that was chromatographed on silica (100 g) Elution with chloroform:hexane (1:5) afforded unreacted while elution with chloroform:hexane (1:4)

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

Procedure: A solution of 1-trifluoroacetoxyadamantane (1.0 g, 4.0 mmole, prepared by reacting adamantan-1-ol with trifluoroacetic anhydride in dry pyridine) in fluorotrichloromethane (10 ml), containing m-dinitrobenzene (80 mg, 0.48 mmole), was treated with trifluoromethyl hypofluorite (4.5 mmole) at -25° for 24 hours, air being recrystallization admitted to the reaction vessel during this time. The product was recovered in a similar manner to that described in Example 3 and was chromatographed on silica (100 g). Elution with chloroform:hexane (1:5) afforded unreacted starting material (152 mg), while elution with chloroform:hexane (1:4) gave liquid 3-fluoro-1-trifluoroacetoxyadamantane (489 mg) which appeared homogeneous by g.l.c. This product sublimed at 70° (bath)/1 mm Hg to give a crystalline solid m.p. 28°-32°; νmax (film) 1780 cm-1 ; PMR 1.5-2.6 (m, adamantyl protons); FMR φ* + 76.2 (s, CF3COO--) and + 133.5 (broad s) ppm. air being recrystallization The product was recovered in a similar manner to that was chromatographed on silica (100 g) Elution with chloroform:hexane (1:5) afforded unreacted while elution with chloroform:hexane (1:4)

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

Procedure: A well-stirred solution of 3β, 17β-di(trifluoroacetoxy)-5α-androstane (2.5 g, 5.15 mmole, prepared by treatment of 5α-androstane-3β,17β-diol with trifluoroacetic anhydride in pyridine), nitrobenzene (800 mg, 6.5 mmole) and sodium trifluoroacetate (10 g, 73.5 mmole) in fluorotrichloromethane (45 ml) was treated with trifluoromethyl hypofluorite (8.5 mmole) at -20° for 2.5 hours, air being admitted to the reaction vessel during this time. Thereafter the solution was purged with nitrogen and the solvent was removed in vacuo. The residue was dissolved in chloroform and the resulting solution was washed with aqueous sodium bicarbonate and water and was then dried, whereafter the product was chromatographed on silica gel (125 g). Elution with chloroform:hexane (3:7) gave unreacted starting material (308 mg), while subsequent elution with chloroform:hexane (7:13) gave 3β,17β-di(trifluoroacetoxy)-9α-fluoro-5α-androstane (1.02 g), which crystallised from hexane as prisms (917 mg) m.p. 140°-142°; [α] D24 -22° (c 1.47, CHCl3). (Found C,55.10; H,5.78; F,26.35%;m/e 502. C33H29O4F7 requires C,54.97; H,5.82; F,26.47%; M+ 502). Thereafter the solution was purged with nitrogen the solvent was removed in vacuo The residue was dissolved in chloroform the resulting solution was washed with aqueous sodium bicarbonate and water was then dried, whereafter the product was chromatographed on silica gel (125 g) Elution with chloroform:hexane (3:7) gave unreacted while subsequent elution with chloroform:hexane (7:13)

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

Procedure: A well-stirred solution of 3β, 17β-di(trifluoroacetoxy)-5α-androstane (2.5 g, 5.15 mmole, prepared by treatment of 5α-androstane-3β,17β-diol with trifluoroacetic anhydride in pyridine), nitrobenzene (800 mg, 6.5 mmole) and sodium trifluoroacetate (10 g, 73.5 mmole) in fluorotrichloromethane (45 ml) was treated with trifluoromethyl hypofluorite (8.5 mmole) at -20° for 2.5 hours, air being admitted to the reaction vessel during this time. Thereafter the solution was purged with nitrogen and the solvent was removed in vacuo. The residue was dissolved in chloroform and the resulting solution was washed with aqueous sodium bicarbonate and water and was then dried, whereafter the product was chromatographed on silica gel (125 g). Elution with chloroform:hexane (3:7) gave unreacted starting material (308 mg), while subsequent elution with chloroform:hexane (7:13) gave 3β,17β-di(trifluoroacetoxy)-9α-fluoro-5α-androstane (1.02 g), which crystallised from hexane as prisms (917 mg) m.p. 140°-142°; [α] D24 -22° (c 1.47, CHCl3). (Found C,55.10; H,5.78; F,26.35%;m/e 502. C33H29O4F7 requires C,54.97; H,5.82; F,26.47%; M+ 502). Thereafter the solution was purged with nitrogen the solvent was removed in vacuo The residue was dissolved in chloroform the resulting solution was washed with aqueous sodium bicarbonate and water was then dried, whereafter the product was chromatographed on silica gel (125 g) Elution with chloroform:hexane (3:7) gave unreacted while subsequent elution with chloroform:hexane (7:13)

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

Procedure: A solution of 1-trifluoroacetoxyadamantane (1.0 g, 4.0 mmole, prepared by reacting adamantan-1-ol with trifluoroacetic anhydride in dry pyridine) in fluorotrichloromethane (10 ml), containing m-dinitrobenzene (80 mg, 0.48 mmole), was treated with trifluoromethyl hypofluorite (4.5 mmole) at -25° for 24 hours, air being admitted to the reaction vessel during this time. The product was recovered in a similar manner to that described in Example 3 and was chromatographed on silica (100 g). Elution with chloroform:hexane (1:5) afforded unreacted starting material (152 mg), while elution with chloroform: hexane (1:4) gave liquid 3-fluoro-1-trifluoroacetoxyadamantane (489 mg) which appeared homogeneous by g.l.c. This product sublimed at 70° (bath)/1 mm Hg to give a crystalline solid m.p. 28°-32°; vmax (film) 1780 cm-1 ; PMR 1.5-2.6 (m, adamantyl protons); FMR φ*+76.2 (s, CF3COO--) and +133.5 (broad s) ppm. The product was recovered in a similar manner to that was chromatographed on silica (100 g) Elution with chloroform:hexane (1:5) afforded unreacted while elution with chloroform: hexane (1:4)

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

Procedure: According to such a synthesis an enol-ether function (2) is generated in the molecule of erythromycin A (1) and subsequently the N-dimethyl group of desosamine is protected as N-oxide (3) to avoid the partial or total N-demethylation of the basic sugar during the fluorination; fluorination of (3) with trifluoromethyl hypofluorite or perchloryl fluoride, followed by hydrogenolysis, gives (8S)-8-fluoroerythromycin A (5). As a matter of fact, by operating according to the disclosure of the second Application erythromycin A can be converted into (8S)-8-fluoroerythromycin A, with a yield of about 35% in four subsequent steps (scheme II):