iodoform

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:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Amino-4-(trifluoromethyl)benzoic acid (commercially available) (6.5 g, 31.7 mmol) and triiodomethane (37.4 g, 95.1 mmol) were dissolved in THF (300 ml). The reaction mixture was heated to 80° C. and then butyl nitrite (5.56 ml, 47.6 mmol) was added slowly at this temperature. Heating was continued at this temperature for 4 hours and then the reaction was concentrated in vacuo to give the crude product. Purification by column chromatography (hexane to 30% EtOAc in hexane). This material was combined with another batch from a similar reaction performed on 2 g of 3-amino-4-(trifluoromethyl)benzoic acid. The combined material was purified by preparative HPLC to give the title compound (6.1 g). MS C8H4F3IO2 requires 316; found 315 (M−H+). Heating the reaction was concentrated in vacuo to give the crude product Purification by column chromatography (hexane to 30% EtOAc in hexane) This material was combined with another batch from a similar reaction The combined material was purified by preparative HPLC

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

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

Procedure: To a heterogeneous mixture of chromium (II) chloride (3.98 g, 32.4 mmol) in tetrahydrofuran (40 mL) at 0° C. was added via syringe pump over 1 hour (in the total absence of light) 4-bromo-benzaldehyde (1.00 g, 5.40 imol) and iodoform (4.25 g, 10.8 mmol) combined as a homogeneous solution in tetrahydrofuran (20 mL). The cold bath was removed, whereupon a quantitative reaction as indicated occurred within 1 hour. The reaction mixture was diluted with 1:1 ether-hexanes (200 mL) then filtered through a short pad of silica gel, concentrated to a solid tainted with residual iodoform. The cold bath was removed, whereupon a quantitative reaction The reaction mixture was diluted with 1:1 ether-hexanes (200 mL) then filtered through a short pad of silica gel concentrated to a solid tainted with residual iodoform

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

Procedure: To a heterogeneous mixture of chromium (II) chloride (3.98 g, 32.4 mmol) in tetrahydrofuran (40 mL) at 0° C. was added via Syringe pump over 1 hour (in the total absence of light) 4-bromo-benzaldehyde (1.00 g, 5.40 mol) and iodoform (4.25 g, 10.8 mmol) combined as a homogeneous solution in tetrahydrofuran (20 mL). The cold bath was removed, whereupon a quantitative reaction as indicated occurred within 1 hour. The reaction mixture was diluted with 1:1 ether-hexanes (200 mL) then filtered through a short pad of silica gel, concentrated to a solid tainted with residual iodoform. The cold bath was removed, whereupon a quantitative reaction The reaction mixture was diluted with 1:1 ether-hexanes (200 mL) then filtered through a short pad of silica gel concentrated to a solid tainted with residual iodoform

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

Procedure: To a suspension of CrCl2 (454 mg, 3.75 mmol, 7.0 eq.) in THF (1.5 mL) at 23° C. was added dropwise a solution of (E)-methyl 10-iododec-9-enoate (100 mg, 0.537 mmol, 1.0 eq.) and iodoform (422 mg, 1.07 mmol, 2.0 eq.) in dioxane (9.2 mL). After stirring for 12 h, the reaction mixture was diluted with Et2O (10 mL) and poured into water (10 mL). The layers were separated and the aqueous layer was extracted with Et2O (3×15 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, and concentrated in vacuo. Purification of the crude product by flash chromatography (hexanes→hexanes:EtOAc 9:1) provided 10-iodo-9-decenoate methyl ester as a yellow oil (105 mg, 0.337 mmol, 63%). 1H NMR indicated an E:Z ratio of 10:1. The layers were separated the aqueous layer was extracted with Et2O (3×15 mL) The combined organic extracts were washed with brine (10 mL) dried over MgSO4 concentrated in vacuo Purification of the crude product by flash chromatography (hexanes→hexanes:EtOAc 9:1)

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

Procedure: To a heterogeneous mixture of chromium (II) chloride (3.98 g, 32.4 mmol) in tetrahydrofuran (40 mL) at 0° C. was added via syringe pump over 1 hour (in the total absence of light) 4-bromo-benzaldehyde (1.00 g, 5.40 mmol) and iodoform (4.25 g, 10.8 mmol) combined as a homogeneous solution in tetrahydrofuran (20 mL). The cold bath was removed, whereupon a quantitative reaction as indicated occurred within 1 hour. The reaction mixture was diluted with 1:1 ether-hexanes (200 mL) then filtered through a short pad of silica gel, concentrated to a solid tainted with residual iodoform. The cold bath was removed, whereupon a quantitative reaction The reaction mixture was diluted with 1:1 ether-hexanes (200 mL) then filtered through a short pad of silica gel concentrated to a solid tainted with residual iodoform

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

Procedure: To a suspension of 7-bromo-2,3-dihydro-1H-[1,8]naphthyridin-4-one (1.5 g) in anhydrous tetrahydrofuran (195 mL) was added a solution of CrCl2 (6.79 g, 8.35 eq) and CHI3 (5.55 g, 2.13 eq) in anhydrous tetrahydrofuran (66 mL). The reaction was stirred at room temperature for 16 hours, diluted with methylene chloride (300 mL), and then washed with saturated NaHCO3 (300 mL). The aqueous phase was extracted twice with methylene chloride (100 mL) and the combined organic layers were washed with brine and then dried over Na2SO4. The solution was filtered and concentrated under reduced pressure. Silica gel chromatography using a gradient of 0-30% ethyl acetate/hexane as the eluting solvent gave the title compound as a yellow solid (27% yield). Alkene geometry was determined by nOe. LCMS: m/z=352 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 2.69 (t, J=6.0 Hz, 2H), 3.43-3.51 (m, 2H), 5.25 (bs, 1H), 6.23 (s, 1H), 6.74 (d, J=8.0 Hz, 1H), 8.19 (d, J=8.0 Hz, 1H). washed with saturated NaHCO3 (300 mL) The aqueous phase was extracted twice with methylene chloride (100 mL) the combined organic layers were washed with brine dried over Na2SO4 The solution was filtered concentrated under reduced pressure

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

Procedure: To a suspension of 7-bromo-2,3-dihydro-1H-[1,8]naphthyridin-4-one (1.5 g) in anhydrous tetrahydrofuran (195 mL) was added a solution of CrCl2 (6.79 g, 8.35 eq) and CHI3 (5.55 g, 2.13 eq) in anhydrous tetrahydrofuran (66 mL). The reaction was stirred at room temperature for 16 hours, diluted with methylene chloride (300 mL), and then washed with saturated NaHCO3 (300 mL). The aqueous phase was extracted twice with methylene chloride (100 mL) and the combined organic layers were washed with brine and then dried over Na2SO4. The solution was filtered and concentrated under reduced pressure. Silica gel chromatography using a gradient of 0-30% ethyl acetate/hexane as the eluting solvent gave the title compound as a yellow solid (27% yield). Alkene geometry was determined by nOe. LCMS: m/z=352 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 2.69 (t, J=6.0 Hz, 2H), 3.43-3.51 (m, 2H), 5.25 (bs, 1H), 6.23 (s, 1H), 6.74 (d, J=8.0 Hz, 1H), 8.19 (d, J=8.0 Hz, 1H). washed with saturated NaHCO3 (300 mL) The aqueous phase was extracted twice with methylene chloride (100 mL) the combined organic layers were washed with brine dried over Na2SO4 The solution was filtered concentrated under reduced pressure

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

Procedure: To a solution of 1,1-dimethylethyl 7-[(4-amino-2-fluorophenyl)oxy]-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (E274, Step 2) (0.5 g, 1.34 mmol) and iodoform (1 g, 2.69 mmol) in tetrahydrofuran (10 ml) was added dropwise tert-butyl nitrite (0.32 ml, 2.69 mmol). The reaction was then heated at reflux for 1 hour, cooled and concentrated in vacuo and resulting residue was purified by column chromatography eluting with a mixture of ethyl acetate:pentane (1:10) to afford the title compound. MS (ES+) m/e 384 [M−COOtBu]+. The reaction was then heated at reflux for 1 hour cooled concentrated in vacuo resulting residue was purified by column chromatography eluting with a mixture of ethyl acetate:pentane (1:10)