Name: 7758-89-6|Copper(I) chloride|99%
Brand: Ambeed
SKU: A631746
Price: 6.0 USD
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1
[ 7758-89-6 ]
[ 586-77-6 ]
[ 33403-21-3 ]
[ 91934-94-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With ammonium chloride; iodine; magnesium; In tetrahydrofuran;	Step 3. 3,3-Ethylenedioxy-5alpha-hydroxy-11beta-[4-(N,N-dimethylamino)phenyl]-17beta-cyano-17alpha-trimethylsilyloxyestr-9(10)-ene (4): Magnesium (2.6 g, 107 mmol) was added to a 1.0 L, 3-neck flask equipped with a magnetic stir bar, addition funnel and a condenser. A crystal of iodine was added followed by dry THF (100 mL) and a few drops of 1,2-dibromoethane. The mixture was stirred under nitrogen and heated in a warm water bath until evidence of reaction was observed. A solution of 4-bromo-N,N-dimethylaniline (19.6 g, 98 mmol) in dry THF (100 mL) was then added dropwise over a period of 20 min. and the mixture stirred for an additional 1.5 hours. Solid copper (I) chloride (1 g, 10.1 mmol) was added followed 30 minutes later by a solution of the 5alpha-,10alpha-epoxide (3, 8.4 g, 19.55 mmol) in dry THF (10 mL). The mixture was stirred at room temperature for 1 hr., then quenched by the addition of saturated NH4Cl solution (100 mL). With vigorous stirring, air was drawn through the reaction mixture for 30 minutes. The mixture was diluted with ether (250 mL) and the layers allowed to separate. The THF/ether solution was washed with 10% NH4Cl solution (3), 2 N NH4OH solution (3) and brine (1*). The organic layers were combined, dried over Na2SO4, filtered and concentrated in vacuo to give the crude product. Crystallization of the crude product from ether gave 8.6 g of the pure product 4 as a white solid in 80% yield; m.p.=222-224 C. dec. FTIR (KBr, diffuse reflectance) numax 3221, 2951, 2232, 1613, 1517 and 1253 cm-1. NMR (CDCl3) delta 0.20 (s, 9H, OSiMe3), 0.5 (s, 3H, C18-CH3), 2.83 (s, 6H, NMe2), 3.9 (m, 4H, OCH2CH2O), 4.3 (m, 1H, C11alpha-CH), 6.63 (d, J=9 Hz, 2H, 3',5' aromatic-CH's) and 7.03 (d, J=9 Hz, 2',6' aromatic-CH's).

Reference： [1]Patent: US6900193,2005,B1

2
[ 7758-89-6 ]
[ 198414-18-5 ]
[ 586-77-6 ]
[ 198414-19-6 ]

Yield	Reaction Conditions	Operation in experiment
46.1%	With lithium aluminium tetrahydride; ammonium chloride; iodine; In tetrahydrofuran; dichloromethane; acetone;	Step 5. 3,3-Ethylenedioxy-5alpha-hydroxy-11beta-[4-(N,N-dimethylamino)phenyl]-17alpha-trimethylsilyloxy-21-methyl-19-norpregn-9(10)-en-20-one (25): Mg (2.80 g, 116.2 mmol), which was washed with 0.1 N HCl, then H2O and acetone and dried in vacuo, was weighed into dry round-bottomed flask equipped with a reflux condenser. A small crystal of iodine was added and the system was flushed with nitrogen and flame-dried. The flask was cooled to room temperature and 68.5 mL of THF distilled from LAH was added via syringe. 1,2-Dibromoethane (approx. 0.5 mL) was added and the mixture was stirred at room temperature. After bubbling began and the color of I2 disappeared, a solution of 4-bromo-N,N-dimethylaniline (20.43 g, 102.1 mmol) in THF (34 mL) was added via syringe. The mixture was stirred until most the Mg had reacted. <strong>[7758-89-6]Copper (I) chloride</strong> (1.13 g, 114.2 mmol) was added as a solid and stirred for 20 min. The crude epoxide (24) (7.33 g, 15.91 mmol) in THF (49 mL) was then added using a syringe. The reaction mixture was stirred at room temperature for 30 min, at which time the reaction was complete by TLC (2% acetone/CH2Cl2). Saturated NH4Cl solution (25 mL) was added and stirred for 30 min while air was pulled through by slight vacuum. The mixture was diluted with H2O, extracted with CH2Cl2 (3), washed with H2O (2) and brine, dried over Na2SO4, and evaporated under reduced pressure. The residue was purified by flash chromatography using 3% acetone/CH2Cl2) to afford 4.27 g of the pure product (25) in 46.1% yield. IR (KBr, diffuse reflectance) numax 3531, 2940, 1708, 1614, and 1518 cm-1. NMR (CDCl3) delta 0.09 (s, 9H, Si(CH3)3), 0.19 (s, 3H, C18-CH3), 1.02 (t, J=7 Hz, 3H, C21-CH3), 2.88 (s, 6H, N(CH3)2), 3.99 (m, 4H, C3-OCH2CH2O-), 4.26 (br d, 1 H, C11alpha-CH), 6.85 (dd, J=41 Hz, J'=10 Hz, 4H, aromatic-CH). MS (EI) m/z (relative intensity): 581 (M+, 46), 563(34), 391 (37), 134(65) and 121 (100).

Reference： [1]Patent: US6900193,2005,B1

3
[ 7758-89-6 ]
[ 454-81-9 ]
[ 1985-12-2 ]
N-(4-bromophenyl)-5-(trifluoromethyl)-1,3-benzoxazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
140%	With triethylamine; In tetrahydrofuran; methanol;	EXAMPLE 1 N2-(4-Bromophenyl)-5-trifluoromethyl-1,3-benzoxazol-2-amine 4-Bromophenyl isothiocyanate (1.667 g, 7.785 mmol) was added to a solution of <strong>[454-81-9]2-amino-4-trifluoromethylphenol</strong> (1.379 g, 7.785 mmol) in tetrahydrofuran (THF) (100 mL) and the reaction was stirred at room temperature for about 16 hours then at about 50 C. for about another 5 hours. Copper (I) chloride (0.771 g, 7.785 mmol) and triethylamine (1.08 mL, 7.785 mmol) were added, and the mixture was stirred at room temperature for about 72 hours and then at about 50 C. for about another 18 hours. Additional copper (I) chloride (0.385 g) was added and the reaction was stirred at about 60 C. for about another 2 hours. The reaction was concentrated under reduced pressure, dissolved in methanol (200 mL), filtered through a pad of diatomaceous earth and the solvent removed in vacuo to afford N2-(4-bromophenyl)-5-trifluoromethyl-1,3-benzoxazol-2-amine as a brown solid (3.90 g, 140% of theory); RP-HPLC Rt 17.627 min, 77% purity (5% to 85% acetonitrile/0.1 M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; lambda=254 nm; Waters Deltapak C18, 300 A, 5 mum, 150*3.9 mm column); and m/z 354.9 and 356.9 (M-H)-.
140%	With triethylamine; In tetrahydrofuran; methanol;	EXAMPLE 1 N2-(4-Bromophenyl)-5-trifluoromethyl-1,3-benzoxazol-2-amine 4-Bromophenyl isothiocyanate (1.667 g, 7.785 mmol) was added to a solution of <strong>[454-81-9]2-amino-4-trifluoromethylphenol</strong> (1.379 g, 7.785 mmol) in tetrahydrofuran (THF) (100 mL) and the reaction was stirred at room temperature for about 16 hours then at about 50 C. for about another 5 hours. Copper (I) chloride (0.771 g, 7.785 mmol) and triethylamine (1.08 mL, 7.785 mmol) were added, and the mixture was stirred at room temperature for about 72 hours and then at about 50 C. for about another 18 hours. Additional copper (I) chloride (0.385 g) was added and the reaction was stirred at about 60 C. for about another 2 hours. The reaction was concentrated under reduced pressure, dissolved in methanol (200 mL), filtered through a pad of diatomaceous earth and the solvent removed in vacuo to afford N2-(4-bromophenyl)-5-trifluoromethyl-1,3-benzoxazol-2-amine as a brown solid (3.90 g, 140% of theory); RP-HPLC Rt 17.627 min, 77% purity (5% to 85% acetonitrile/0.1M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; lambda=254 nm; Waters Deltapak C18, 300 A, 5 mum, 150*3.9 mm column); and m/z 354.9 and 356.9 (M-H)-.

Reference： [1]Patent: US2003/9034,2003,A1
[2]Patent: US2003/109714,2003,A1

4
[ 7758-89-6 ]
aqueous ammonium acetate [ No CAS ]
[ 95-84-1 ]
[ 1985-12-2 ]
[ 461699-48-9 ]

Yield	Reaction Conditions	Operation in experiment
11%	With triethylamine; In methanol; n-heptane; dichloromethane; ethyl acetate; acetonitrile;	EXAMPLE 2 N2-(4-Bromophenyl)-5-methyl-1,3-benzoxazol-2-amine 4-Bromophenyl isothiocyanate (2.0 g, 9.34 mmol) was added to a solution of 2-amino-4-methylphenol (1.15 g, 9.34 mmol) in acetonitrile (100 mL) and the reaction was stirred at room temperature for about 16 hours. The formation of the intermediate N-(4-bromophenyl)-N'-(2-hydroxy-5-methylphenyl)thiourea was complete, as analyzed by RP-HPLC Rt 13.010 min, 98% purity (5% to 85% acetonitrile/0.1 M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; lambda=254 nm; Deltapak C18, 300 A, 5 mum, 1503.9 mm column). <strong>[7758-89-6]Copper (I) chloride</strong> (0.925 g, 9.34 mmol) and triethylamine (1.29 mL, 9.34 mmol) were added, and the mixture was stirred at room temperature for about 6 days. The reaction was concentrated under reduced pressure, dissolved in methanol (200 mL), filtered through a pad of diatomaceous earth and the solvent removed in vacuo to afford a brown solid. The solid was dissolved in dichloromethane (200 mL), washed with water (2200 mL), dried over anhydrous sodium sulfate and absorbed onto silica (10 mL). The product was purified by chromatography through a silica pad using 10% ethyl acetate in n-heptane as the eluent to afford N2-(4-bromophenyl)-5-methyl-1,3-benzoxazol-2-amine as a yellow solid (0.30 g, 11%); RP-HPLC Rt 16.451 min, 95% purity (5% to 85% acetonitrile/0.1 M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; lambda=254 nm; Deltapak C18, 300 A, 5 mum, 150*3.9 mm column); and m/z 302.9 and 304.9 (MH+).
11%	With triethylamine; In methanol; n-heptane; dichloromethane; ethyl acetate; acetonitrile;	EXAMPLE 2 N2-(4-Bromophenyl)-5-methyl-1,3-benzoxazol-2-amine 4-Bromophenyl isothiocyanate (2.0 g, 9.34 mmol) was added to a solution of 2-amino-4-methylphenol (1.15 g, 9.34 mmol) in acetonitrile (100 mL) and the reaction was stirred at room temperature for about 16 hours. The formation of the intermediate N-(4-bromophenyl)-N'-(2-hydroxy-5-methylphenyl)thiourea was complete, as analyzed by RP-HPLC Rt 13.010 min, 98% purity (5% to 85% acetonitrile/0.1M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; lambda=254 nm; Deltapak C18, 300 A, 5 mum, 1503.9 mm column). <strong>[7758-89-6]Copper (I) chloride</strong> (0.925 g, 9.34 mmol) and triethylamine (1.29 mL, 9.34 mmol) were added, and the mixture was stirred at room temperature for about 6 days. The reaction was concentrated under reduced pressure, dissolved in methanol (200 mL), filtered through a pad of diatomaceous earth and the solvent removed in vacuo to afford a brown solid. The solid was dissolved in dichloromethane (200 mL), washed with water (2200 mL), dried over anhydrous sodium sulfate and absorbed onto silica (10 mL). The product was purified by chromatography through a silica pad using 10% ethyl acetate in n-heptane as the eluent to afford N2-(4-bromophenyl)-5-methyl-1,3-benzoxazol-2-amine as a yellow solid (0.30 g, 11%); RP-HPLC Rt 16.451 min, 95% purity (5% to 85% acetonitrile/0.1M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; lambda=254 nm; Deltapak C18, 300 A, 5 mum, 150*3.9 mm column); and m/z 302.9 and 304.9 (MH+).

Reference： [1]Patent: US2003/9034,2003,A1
[2]Patent: US2003/109714,2003,A1

5
[ 7758-89-6 ]
jones' reagent [ No CAS ]
[ 925-90-6 ]
[ 54947-74-9 ]

Yield	Reaction Conditions	Operation in experiment
2.14 g (59%)	With ammonium chloride; lithium chloride; In tetrahydrofuran; H2SO4 (aq); diethyl ether; acetone;	(R)-4-Methyl-octanoic acid 136 Lithium chloride (0.39 g, 9.12 mmol) and copper (I) chloride (0.61 g, 4.56 mmol) were combined in 45 mL THF at ambient temperature and stirred 15 minutes, then cooled to 0 C. at which time ethyl magnesium bromide (1 M solution in THF, 45 mL, 45 mmol) was added. (S)-citronellyl bromide (5.0 g, 22.8 mmol) was added dropwise and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The reaction was quenched by cautious addition of sat. NH4Cl (aq), and stirred with Et2O and sat. NH4Cl (aq) for 30 minutes. The phases were separated and the organic phase dried (MgSO4) and concentrated. The crude product was used without purification. To a solution of alkene 135 (3.8 g, 22.8 mmol) in 50 mL acetone at 0 C. was added Jones' reagent (2.7 M in H2SO4 (aq), 40 mL, 108 mmol) and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The mixture was partitioned between Et2O and H2O, the phases were separated, and the organic phase washed with brine, dried (MgSO4), and concentrated. The residue was purified by flash chromatography (8:1 hexanes:EtOAc) to afford 2.14 g (59%) of acid 136 as a colorless oil: LRMS: m/z 156.9 (M+); 1H NMR (CDCl3): delta 2.33 (m, 2H), 1.66 (m, 1H), 1.43 (m, 2H), 1.23 (m, 5H), 1.10 (m, 1H), 0.86 (m, 6H). Jones' reagent was prepared as a 2.7M solution by combining 26.7 g CrO3, 23 mL H2SO4, and diluting to 100 mL with H2O.
2.14 g (59%)	With ammonium chloride; lithium chloride; In tetrahydrofuran; H2SO4 (aq); diethyl ether; acetone;	(R)-4-Methyl-octanoic acid 136 Lithium chloride (0.39 g, 9.12 mmol) and copper (I) chloride (0.61 g, 4.56 mmol) were combined in 45 ml THF at ambient temperature and stirred 15 minutes, then cooled to 0 C. at which time ethylmagnesium bromide (1 M solution in THF, 45 mL, 45 mmol) was added. (S)-citronellyl bromide (5.0 g, 22.8 mmol) was added dropwise and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The reaction was quenched by cautious addition of sat. NH4Cl (aq), and stirred with Et2O and sat. NH4Cl (aq) for 30 minutes. The phases were separated and the organic phase dried (MgSO4) and concentrated. The crude product was used without purification. To a solution of alkene 135 (3.8 g, 22.8 mmol) in 50 mL acetone at 0 C. was added Jones' reagent (2.7 M in H2SO4 (aq), 40 mL, 108 mmol) and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The mixture was partitioned between Et2O and H2O, the phases were separated, and the organic phase washed with brine, dried (MgSO4), and concentrated. The residue was purified by flash chromatography (8:1 hexanes:EtOAc) to afford 2.14 g (59%) of acid 136 as a colorless oil: LRMS: m/z 156.9 (M+); 1H NMR (CDCl3): delta2.33 (m, 2H), 1.66 (m, 1H), 1.43 (m, 2H), 1.23 (m, 5H), 1.10 (m, 1H), 0.86 (m, 6H). Jones' reagent was prepared as a 2.7M solution by combining 26.7 g CrO3, 23 mL H2SO4, and diluting to 100 mL with H2O.
2.14 g (59%)	With ammonium chloride; lithium chloride; In tetrahydrofuran; H2SO4 (aq); diethyl ether; acetone;	EXAMPLE 21 (R)-4-Methyl-octanoic Acid 136 Lithium chloride (0.39 g, 9.12 mmol) and copper (I) chloride (0.61 g, 4.56 mmol) were combined in 45 mL THF at ambient temperature and stirred 15 minutes, then cooled to 0 C. at which time ethyl magnesium bromide (1 M solution in THF, 45 mL, 45 mmol) was added. (S)-citronellyl bromide (5.0 g, 22.8 mmol) was added dropwise and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The reaction was quenched by cautious addition of sat. NH4Cl (aq), and stirred with Et2O and sat. NH4Cl (aq) for 30 minutes. The phases were separated and the organic phase dried (MgSO4) and concentrated. The crude product was used without purification. To a solution of alkene 135 (3.8 g, 22.8 mmol) in 50 mL acetone at 0 C. was added Jones' reagent (2.7 M in H2SO4 (aq), 40 mL, 108 mmol) and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The mixture was partitioned between Et2O and H2O, the phases were separated, and the organic phase washed with brine, dried (MgSO4), and concentrated. The residue was purified by flash chromatography (8:1 hexanes:EtOAc) to afford 2.14 g (59%) of acid 136 as a colorless oil: LRMS: m/z 156.9 (M+); 1H NMR (CDCl3): delta 2.33 (m, 2H), 1.66 (m, 1H), 1.43 (m, 2H), 1.23 (m, 5H), 1.10 (m, 1H), 0.86 (m, 6H). Jones' reagent was prepared as a 2.7M solution by combining 26.7 g CrO3, 23 mL H2SO4, and diluting to 100 mL with H2O.

2.14 g (59%)

With ammonium chloride; lithium chloride; In tetrahydrofuran; H2SO4 (aq); diethyl ether; acetone;

(R)-4-Methyl-octanoic acid 136 Lithium chloride (0.39 g, 9.12 mmol) and copper (I) chloride (0.61 g, 4.56 mmol) were combined in 45 ml THF at ambient temperature and stirred 15 minutes, then cooled to 0 C. at which time ethylmagnesium bromide (1 M solution in THF, 45 mL, 45 mmol) was added. (S)-citronellyl bromide (5.0 g, 22.8 mmol) was added dropwise and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The reaction was quenched by cautious addition of sat. NH4Cl (aq), and stirred with Et2O and sat. NH4Cl (aq) for 30 minutes. The phases were separated and the organic phase dried (MgSO4) and concentrated. The crude product was used without purification. To a solution of alkene 135 (3.8 g, 22.8 mmol) in 50 mL acetone at 0 C. was added Jones' reagent (2.7 M in H2SO4 (aq), 40 mL, 108 mmol) and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The mixture was partitioned between Et2O and H2O, the phases were separated, and the organic phase washed with brine, dried (MgSO4), and concentrated. The residue was purified by flash chromatography (8:1 hexanes:EtOAc) to afford 2.14 g (59%) of acid 136 as a colorless oil: LRMS: m/z 156.9 (M+); 1H NMR (CDCl3): delta 2.33 (m, 2H), 1.66 (m, 1H), 1.43 (m, 2H), 1.23 (m, 5H), 1.10 (m, 1H), 0.86 (m, 6H). Jones' reagent was prepared as a 2.7M solution by combining 26.7 g CrO3, 23 mL H2SO4, and diluting to 100 mL with H2O.

Reference： [1]Patent: US2003/176504,2003,A1
[2]Patent: US2003/181523,2003,A1
[3]Patent: US2002/72533,2002,A1
[4]Patent: US2004/186177,2004,A1

6
[ 7758-89-6 ]
[ 14543-43-2 ]
[ 1985-12-2 ]
[ 461699-30-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In methanol; acetonitrile;	EXAMPLE 5 N2-(4-Bromophenyl)-5-cyano-1,3-benzoxazol-2-amine 4-Bromophenyl isothiocyanate (2.93 g, 0.0137 mol) was added to a solution of <strong>[14543-43-2]3-amino-4-hydroxybenzonitrile</strong> (1.84 g, 0.0137 mol) in acetonitrile (140 mL) at room temperature. The mixture was stirred for about 16 hours prior to the addition of copper (I) chloride (1.36 g, 0.0137 mol) and triethylamine (1.9 mL, 0.0137 mol). The mixture was stirred for about another 16 hours and the solvent was removed under reduced pressure. The solid was dissolved in methanol (100 mL), filtered through a pad of diatomaceous earth, and washed with additional methanol (2*50 mL). The brownish filtrate was left to stand at about 4 C. for about 3 days and the resulting precipitate was collected by filtration to afford N2-(4-bromophenyl)-5-cyano-1,3-benzoxazol-2-amine (2.4 g, 0.0076 mol, 55%); RP-HPLC Rt 11.1 min, 92% purity (Delta Pak C18, 5 mum, 300 A, 15 cm; 5%-95% acetonitrile-0.1 M ammonium acetate over 10 min, 1 mL/min); and 1H NMR (400 MHz, d6-DMSO) 7.59 (3H, m), 7.72 (3H, m), 7.97 (1H, s), and 11.12 (1H, s).
	With triethylamine; In methanol; acetonitrile;	EXAMPLE 5 N2-(4-Bromophenyl)-5-cyano-1,3-benzoxazol-2-amine 4-Bromophenyl isothiocyanate (2.93 g, 0.0137 mol) was added to a solution of <strong>[14543-43-2]3-amino-4-hydroxybenzonitrile</strong> (1.84 g, 0.0137 mol) in acetonitrile (140 mL) at room temperature. The mixture was stirred for about 16 hours prior to the addition of copper (I) chloride (1.36 g, 0.0137 mol) and triethylamine (1.9 mL, 0.0137 mol). The mixture was stirred for about another 16 hours and the solvent was removed under reduced pressure. The solid was dissolved in methanol (100 mL), filtered through a pad of diatomaceous earth, and washed with additional methanol (2*50 mL). The brownish filtrate was left to stand at about 4 C. for about 3 days and the resulting precipitate was collected by filtration to afford N2-(4-bromophenyl)-5-cyano-1,3-benzoxazol-2-amine (2.4 g, 0.0076 mol, 55%); RP-HPLC Rt 11.1 min, 92% purity (Delta Pak C18, 5 mum, 300 A, 15 cm; 5%-95% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min); and 1H NMR (400 MHz, d6-DMSO) 7.59 (3H, m), 7.72 (3H, m), 7.97 (1H, s), and 11.12 (1H, s).

Reference： [1]Patent: US2003/9034,2003,A1
[2]Patent: US2003/109714,2003,A1

Yield	Reaction Conditions	Operation in experiment
76%		G. Cuprous chloride--76% yield
		EXAMPLE 15 (17R)-11-beta-[4-(1-methylethoxy)phenyl]-spiro(estra-4,9-dien-17,2'-(5H)-furan)-3-one Stage A: (Z) (1,2-ethanediyl) cyclic acetal of 5-alpha,17-beta-dihydroxy-11-beta-[4-(1-methylethoxy)phenyl]-17-alpha-3-(tetrahydro-2H-2-pyrannyloxy)-1-propenyl-estr-9-en-3-one The operation is done as in stage B of example 8, utilizing 2.5 g of the product obtained as indicated in stage A of example 8, 110 mg of cuprous chloride and 35 cm3 of the magnesium compound prepared as at example 3, starting with 1-bromo-4-(1-methylethoxy)benzene. 6.764 g of crude product is obtained, which is chromatographed on silica (eluent:
		EXAMPLE IV Preparation of 2-(2',4'-Dichlorophenyl)-5,5-dimethyl-1,3-cyclohexanedione A fresh sample of cuprous chloride was prepared by slowly adding a solution of 2.09 g of sodium bisulfite and 1.38 g of NaOH in 20 ml of water to a solution of 9.86 g CuSO4.5H2 O and 2.75 g NaCl in 100 ml of hot water.

		EXAMPLE 8 28 g. of 3-amino-5-acetylaminomethyl-2,4,6-triiodobenzoic acid is suspended in 450 ml. of water, and the suspension is combined dropwise with a solution of 4.5 g. of sodium nitrite in 24 ml. of water under cooling between 0 and +5 C. After setting a pH of 2.5 by the addition of dilute sulfuric acid, the batch is stirred for 2 hours in an ice bath. Under cooling, 30 ml. of a 30% sodium hydroxide solution is then added dropwise within one hour. In the meantime, a hot solution of 45 g. of copper(II) sulfate pentahydrate and 11.7 g. of sodium chloride in 160 ml. of water is combined with a solution of 9.6 g. of sodium bisulfite and 6.3 g. of caustic soda in 80 ml. of water and, after cooling, the freshly precipitated copper(I) chloride is vacuum-filtered. The latter is washed with water, suspended in 80 ml. of water, and dissolved by the addition of 30 g. of potassium cyanide.
		B. To a portion of the liquid sorbent was added anhydrous pyridine in the amount of 30 mole percent, based on copper in the liquid sorbent. The mixture was stirred at 25 C. until precipitation of cuprous chloride had been completed. A solution of the pyridine-aluminum chloride adduct in the liquid sorbent was separated from the precipitated cuprous chloride.
		EXAMPLE 2 To a 5 ml. portion of a liquid sorbent prepared by the procedure described in Example 1A, which contained 13.5 mmol of copper, was added a solution of 244 mg. (2.02 mmol) of N,N-dimethylaniline in 2 ml. of anhydrous toluene. The resulting mixture was heated at 80 C. and then filtered to separate precipitated cuprous chloride from the liquid sorbent that contained 17.4 mole percent, based on copper in the sorbent, of the N,N-dimethylaniline-aluminum chloride adduct.
		EXAMPLE 3 To a 5 ml. portion of a liquid sorbent prepared by the procedure described in Example 1A, which contained 12.7 mmol of copper, was added 2.05 mmol of ammonia. The resulting mixture was heated at 75 C. for one hour and then filtered to separate precipitated cuprous chloride from the liquid sorbent that contained 19.1 mole percent of the ammonia-aluminum chloride adduct, based on copper in the liquid sorbent.
		EXAMPLE 6 To a 5 ml. portion of a liquid sorbent prepared by the procedure described in Example 1A, which contained 13.5 mmol of copper, was added a solution of 217.6 mg (2.02 mmol) of triethylamine in 2 ml. of anhydrous toluene. The reaction mixture was heated at 85 C. for 4 hours and then filtered to separate precipitated cuprous chloride from the liquid sorbent that contained 18.9 mole percent of triethylamine-aluminum chloride adduct, based on copper in the liquid sorbent.
		EXAMPLE 35 Preparation of the 2:1 complex of [bis(4-Fluorophenyl)]methyl(1H-1,2,4-triazol-1-ylmethyl)silane and Curpic Chloride A mixture of 1.0 g (0.0032 mol) of [bis(4-fluorophenyl)]methyl(1H-1,2,4-triazol-1-ylmethyl)silane and 0.2 g (0.0016 mol) of cupric chloride in 30 ml of tetrahydrofuran was refluxed under N2 for 30 minutes and evaporated to leave the title complex as a bluegreen glass: no distinct m.p.; ir (Nujol) 1580, 1490, 1230, 1160, 1110, 830, 785 cm-1. The 1:1 complex with cuprous chloride was prepared similarly to give a dark green glass: no distinct m.p.; ir as above.
		EXAMPLE 25 This Example illustrates the preparation of Compound 39 in Table I. Concentrated hydrochloric acid (0.47 ml) and water (0.47 ml) were added together to Compound 38 (600 mg) with constant stirring and the mixture cooled to 0 C. in an ice/salt bath. A solution of sodium nitrite (133 mg) in water (0.3 ml) was added with stirring whilst maintaining the temperature below 5 C. A cuprous chloride solution was prepared by dissolving copper sulphate (6.25 g) and sodium chloride (1.625 g) in water (20 ml) and mixing 1.1 mls of this solution with 2.2 mls of a solution prepared from sodium bisulphate (2.65 g), sodium hydroxide (1.75 g) and water (20 ml).
		(c) The medium obtained at the end of step (b) was cooled to a temperature of from 0 C. to -5 C., and 27 g (0.2 mole) of copper chloride were added slowly while keeping the temperature of the medium below or at +5 C. during the addition. Then the reaction medium was agitated for one hour at the ambient temperature. While cooling to about 10 C., 15 ml of water and 25 ml of a 37% concentrated aqueous solution of hydrochloric acid were added. The cuprous chloride precipitate formed was separated by filtration and washed with 10 ml of water.
		EXAMPLE IV Preparation of 2-(2', 4'-Dichlorophenyl)-5,5-dimethyl-1, 3-cyclohexanedione A fresh sample of cuprous chloride was prepared by slowly adding a solution of 2.09 g of sodium bisulfite and 1.38 g of NaOH in 20 ml of water to a solution of 9.86 g CuSO4.5 H2 O and 2.75 g NaCl in 100 ml of hot water.
		Addition of CCl4 according to U.S. Pat. No. 3,454,657 The 3,5-dichloro-alpha-methylstyrene is placed in a 250 ml. vessel equipped with a stirring means and a heating means. A mixture including 18.7 g. (0.1 mole) of 3,5-dichloro-alpha-methylstyrene, as well as 46.2 g. (0.3 mole) of CCl4 and 0.4 g. of cuprous chloride is formed with stirring.
		Addition of CCl4 via U.S. Pat. No. 3,454,657 The 3,5-dichloro-alpha-methylstyrene is placed in a 250 ml. vessel equipped with a stirring means and a heating means. A mixture including 18.7 g. (0.1 mole) of 3,5-dichloro-alpha-methylstyrene, as well as 46.2 g. (0.3 mole) of CCl4 and 0.4 g. of cuprous chloride is formed with stirring.
		EXAMPLE 9 1.4 g of the 5-(p-aminophenoxy)picolinic acid dihydrochloride as obtained in Example 8 was suspended in 22 ml of concentrated hydrochloric acid, and 3 ml of an aqueous solution containing 828 mg of sodium nitrite was added dropwise to the suspension over a period of 1 hour under ice-cooling. 5.4 ml of an aqueous solution containing 760 mg of sodium metabisulfite and 480 mg of sodium hydroxide was added to 11 ml of a warm aqueous solution containing 3.4 g of copper sulfate pentahydrate and 2.9 g of sodium chloride to prepare a cuprous chloride solution.
		EXAMPLE IV Preparation of 2-(2', 4'-Dichlorophenyl)-5,5-dimethyl-1, 3-cyclohexanedione A fresh sample of cuprous chloride was prepared by slowly adding a solution of 2.09 g of sodium bisulfite and 1.38 g of NaOH in 20 ml of water to a solution of 9.86 g CuSO4.5H2 o and 2.75 g NaCl in 100 ml of hot water.
		EXAMPLE 1 Catalyst Preparation: 20 grams of cuprous chloride (CuCl) and 40 grams of tetramethylethylenediamine (TMEDA) are stirred at room temperature in 200 ml of acetone for 3 hours under aerobic conditions (i.e. no attempt is made to exclude atmospheric oxygen). A dark brown solid precipitates and is recovered by filtration, washed with 50 ml of acetone, and dried in the presence of air. 45 grams of catalyst is collected.

8
[ 7758-89-6 ]
[ 638-10-8 ]
[ 931-51-1 ]
ammonium chloride [ No CAS ]
[ 570398-24-2 ]

Yield	Reaction Conditions	Operation in experiment
	With chloro-trimethyl-silane; In tetrahydrofuran; diethyl ether; ethyl acetate; pentane;	Preparation 19 Ethyl 3-cyclohexyl-3-methylbutanoate Trimethylsilyl chloride (1.3 ml, 10.2 mmol), copper (I) chloride (30 mg, 0.3 mmol) and cyclohexylmagnesium chloride (4.6 ml, 2N in diethyl ether, 9.2 mmol) were added slowly to an ice-cooled solution of ethyl 3,3-dimethylacrylate (1 g, 8.5 mmol) in tetrahydrofuran (10 ml). The solution was stirred for 10 minutes, then allowed to warm to room temperature and stirred for an hour. Saturated aqueous ammonium chloride solution (10 ml) was added and the mixture was partitioned between water (10 ml) and diethyl ether (20 ml). The layers were separated and the aqueous phase was extracted with diethyl ether (2*10 ml). The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel using ethyl acetate:pentane(5:95) as eluant to afford the title compound, 1.2 g. 1H-NMR (CDCl3, 400 MHz) delta: 0.75 (m, 8H), 1.05-1.28 (m, 7H), 1.62 (m, 1H), 1.78 (m, 4H), 2.20 (s, 2H), 4.10 (q, 2H).

Reference： [1]Patent: US2003/199522,2003,A1

9
[ 7758-89-6 ]
[ 540-80-7 ]
[ 475215-60-2 ]
(acetone/ice/sodium chloride) CH₂Cl₂ [ No CAS ]
[ 109-63-7 ]
[ 475215-61-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sulfur dioxide; acetic acid; lithium chloride; In 1,4-dioxane; dichloromethane; acetonitrile; pentane;	Step 3 4-Fluoro-2-(2-naphthalen-1-yl-ethoxy)-benzenesulfonyl Chloride To a -10 C. (acetone/ice/sodium chloride) CH2Cl2 solution of 4-fluoro-2-(2-naphthalen-1-yl-ethoxy)-phenylamine (15.0 g, 53.30 mmol) was added boron trifluoride diethyl etherate (19.7 mL, 160.0 mmol) dropwise. Tert-Butyl nitrite (8.30 mL, 69.3 mmol) was then slowly added dropwise. The reaction mixture was allowed to stirred at -10 C. for 30 min. Chilled pentane (150 mL) was then added to precipitate the diazo-salt from CH2Cl2. The diazo-salt was then dissolved in dioxane:acetonitrile (3:1, 150 mL) kept at 0 C. In a three-necked flask to a solution of dioxane (150 mL) and acetic acid (150 mL) at -10 C. was added copper (I) chloride (1.60 g, 16.0 mmol) and LiCl (33.0 g, 319 mmol). Sulfur dioxide (~100 mL) was then condensed into this solution using a -78 C. cold finger. The above diazo-salt solution was then poured into this solution. The reaction was kept at 0 C. for 2 h and then placed into a preheated oil bath at 65 C. for 12 h. The reaction was then cooled and poured into EtOAc (500 mL) and washed with water, and 1 N sodium hydroxide. The organic layer was then dried (MgSO4), filtered and concentrated under reduced pressure to yield 4-fluoro-2-(2-naphthalen-1-yl-ethoxy)-benzenesulfonyl chloride as a yellowish foam (19.90 g, 98%). 1H NMR (CDCl3, 400 MHz) 8.05 (d, 1H), 7.90 (d, 1H), 7.87 (d, 1H), 7.78 (d, 1H), 7.60-6.42 (m, 4H), 6.78-6.64 (m, 2H), 4.21 (t, 2H), 3.79 (t, 2H).

Reference： [1]Patent: US2003/96826,2003,A1

10
[ 475215-88-4 ]
[ 7758-89-6 ]
(acetone/ice/sodium chloride) methylene chloride [ No CAS ]
3-benzyloxy-4-diazenyl-benzoic acid methyl ester [ No CAS ]
[ 109-63-7 ]
[ 475215-89-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; tert.-butylnitrite; sulfur dioxide; acetic acid; lithium chloride; In 1,4-dioxane; dichloromethane; water; acetonitrile; pentane;	Step 3 3-Benzyloxy-4-chlorosulfonyl-benzoic Acid Methyl Ester REFERENCE: J. Org. Chem, 1979,44, 1572-1574. To a -10 C. (acetone/ice/sodium chloride) methylene chloride solution of 4-amino-3-benzyloxy-benzoic acid methyl ester (8.7 g, 33.8 mmol) was added boron trifluoride diethyl etherate (12.4 mL, 101.5 mmol) dropwise. A methylene chloride solution (5.2 mL) of tert-butyl nitrite (4.8 mL, 40.5 mmol) was then slowly added dropwise. The reaction was allowed to stir at -10 C. for approximately 30 min. At this point a small aliquot (2 mL) was removed and concentrated under reduced pressure. 1H NMR showed that the reaction was complete. Chilled pentane (125 mL) was then added to precipitate the diazo-salt from the methylene chloride. The 3-benzyloxy-4-diazenyl-benzoic acid methyl ester was then dissolved in dioxane (~150 mL) and acetonitrile (50 mL) and used without any further manipulation. To a -10 C. (acetone/ice/sodium chloride) solution of dioxane (150 mL) and acetic acid (150 mL) was added copper (I) chloride (0.99 g, 10.5 mmol) and lithium chloride (8.5 g, 201 mmol). Sulfur dioxide (~150 mL) was then condensed into this solution using a -78 C. cold finger. The above solution of 3-benzyloxy-4-diazenyl-benzoic acid methyl ester was then poured into this solution. The reaction was kept at 0 C. for 4-5 h and then placed into a preheated oil bath at 65 C. overnight. The reaction was then cooled and poured into ethyl acetate (600 mL) and washed in succession with water and 1N sodium hydroxide. A final wash with saturated aqueous sodium chloride was done and the organic layer was then dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 3-benzyloxy-4-chlorosulfonyl-benzoic acid methyl ester as a foam. This was used in the next step without further purification. The product moved on TLC to a Rf of 0.5 in 30% ethyl acetate/hexane. 1H NMR (CDCl3) 8.00(d,1H), 7.75(s,1H), 7.67(d,1H), 7.49(d,2H), 7.35(m,3H), 5.35(s,2H), 3.91(s,3H).

Reference： [1]Patent: US2003/96826,2003,A1

11
[ 7758-89-6 ]
jones' reagent [ No CAS ]
[ 925-90-6 ]
[ 171627-77-3 ]
[ 610300-20-4 ]
[ 54947-74-9 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium chloride; lithium chloride; In tetrahydrofuran; H2SO4 (aq); diethyl ether; acetone;	Example 3 (3S,5R)-3-Amino-5-methyl-nonanoic Acid (R)-4-Methyl-octanoic acid. Lithium chloride (0.39 g, 9.12 mmol) and copper (I) chloride (0.61 g, 4.56 mmol) were combined in 45 ml THF at ambient temperature and stirred 15 minutes, then cooled to 0 C. at which time ethylmagnesium bromide (1 M solution in THF, 45 mL, 45 mmol) was added. (S)-citronellyl bromide (5.0 g, 22.8 mmol) was added dropwise and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The reaction was quenched by cautious addition of sat. NH4Cl (aq), and stirred with Et2O and sat. NH4Cl (aq) for 30 minutes. The phases were separated and the organic phase dried (MgSO4) and concentrated. The crude (R)-2,6-dimethyl-dec-2-ene was used without purification. To a solution of (R)-2,6-dimethyl-dec-2-ene (3.8 g, 22.8 mmol) in 50 mL acetone at 0 C. was added Jones' reagent (2.7 M in H2SO4 (aq), 40 mL, 108 mmol) and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The mixture was partitioned between Et2O and H2O, the phases were separated, and the organic phase washed with brine, dried (MgSO4), and concentrated.

Reference： [1]Patent: US2003/195251,2003,A1

12
[ 7758-89-6 ]
[ 345901-66-8 ]
[ 586-77-6 ]
[ 106-93-4 ]
[ 345901-67-9 ]

Yield	Reaction Conditions	Operation in experiment
53.3%	With ammonium chloride; iodine; magnesium; In tetrahydrofuran; water;	Preparation of 3,3-ethylenedioxy-5alpha,17alpha,20-trihydroxy-11beta-[4-(N,N-dimethylamino)phenyl]-21-methoxy-19-norpregn-9-ene (17) A dry 250 mL 3-necked flask was equipped with a stirring bar, a reflux condenser, and two rubber septa. Magnesium (1.18 g, 48.5 mmol) was added and the entire apparatus dried further with a heat gun, under a stream of nitrogen. The apparatus was allowed to cool slightly and one crystal of iodine was added. After cooling completely, 20 mL of dry THF was added, followed by the addition of one drop of 1,2-dibromoethane. A solution of 4-bromo-N,N-dimethylaniline (8.81 g, 44.05 mmol) in THF (10 mL) was added via transfer needle and rinsed with additional THF (10 mL). The mixture was heated gently with a heat gun to reflux to initiate reaction (as evidenced by bleaching of color and consumption of magnesium) and then allowed to stir for a period of 1/2 hr at room temperature. <strong>[7758-89-6]Copper (I) chloride</strong> (480 mg, 4.85 mmol) was added as a solid and stirring was continued for a period of 1/2 hr. A solution of the epoxide (16, 3.58 g, 8.81 mmol) in THF (20 mL) was added via transfer needle and rinsed in with additional THF (10 mL). After stirring for another 2 hr. at room temperature, the reaction was quenched by the addition of saturated NH4Cl solution (70 mL). Air was drawn through the mixture for period of 1/2 hr with vigorous stirring. The resulting mixture was transferred to a separatory funnel, and water and ether were added. The organic and aqueous layers were allowed to separate. The organic fraction was washed again with water (1) and brine (1). The combined ether extracts (3) were dried by filtration through sodium sulfate and evaporated in vacuo to recover 7.7 g of a dark purple oil. The oil was filtered through a short bed of silica (125 g) on a sintered glass funnel. Elution with ether (4200 mL) removed all of the aniline by-products. The product was eluted with EtOAc (8*100 mL). The EtOAc washes were evaporated in vacuo to recover a beige foam. Trituration with pentane produced a solid. The solid was dried overnight under high vacuum to give 2.48 g of 17 as a beige powder in 53.3% yield. A small portion (250 mg) was purified by flash chromatography (5% isopropanol in methylene chloride) for analysis. Only fractions of the highest purity were combined and evaporated to recover a colorless gum. Trituration with pentane produced a solid. The sample was dried in vacuo at 80 C. to recover 56.9 mg of 17 as a white powder; m.p.=120-126 C. (softens). FTIR (KBr, diffuse reflectance): vmax 3487, 2930, 1614, 1559, 1517, 1445, 1374, 1198, and 1120 cm-1. NMR (300 MHZ, CDCl3): delta0.424 (s, 3H, C18-CH3), 2.908 (s, 6H, -N(CH3)2), 3.361 (s, 3H, C21-OCH3), 3.461 (dd, 1H, C21-CH, J1=9.76 Hz, J2=2.79 Hz), 3.527 (dd, 1H, C21-CH, J1=9.76 Hz, J2=6.45 Hz), 3.783 (dd, 1H, C20-CH, J1=6.45 Hz, J2=2.79 Hz), 3.996 (m, 4H, C3-OCH2CH2 O-), 4.210 (d, 1H, C11beta-CH, J=8.70), 6.666 (d, 2H, 3',5'-aromatic CH, J=8.70 Hz) and 7.093 (d, 2H, 2',6'-aromatic CH, J=8.70 Hz). MS (EI) m/z (relative intensity): 527 (M+, 15.1), 509 (14.6), 238 (6.2), 134 (32.4), 121 (100), and 99 (15.1). Anal. Calcd for C31H45NO6.H2O: C, 69.77; H, 8.62; N, 2.62; Found: C, 69.80; H, 8.61; N, 2.43.

Reference： [1]Patent: US2003/60646,2003,A1

13
[ 7758-89-6 ]
[ 527680-64-4 ]
[ 527680-65-5 ]

Yield	Reaction Conditions	Operation in experiment
57%	In pyridine; dichloromethane;	A solution of 1-(2,4-diiodophenoxy)butan-2-ol (1.27 g, 3.0) in pyridine (12 mL) is degassed by repeatedly evacuating the flask then filling with N2. Sodium hydride (60% suspension, 153 mg, 3.8 mmol) is added and the resulting mixture is stirred for 15 min. <strong>[7758-89-6]Copper (I) chloride</strong> (15 mg, 0.15 mmol) is added, and the resulting mixture is heated at 80 C. for 2 h. The reaction is allowed to cool, poured into 1M HCl and extracted three times with CH2Cl2. The combined organic extracts are dried (Na2SO4), filtered and concentrated in vacuo. The resulting material is purified by column chromatography (10% CH2Cl2 in hexanes) to give 2-ethyl-7-iodo-2,3-dihydro-1,4-benzodioxine as a clear oil (493 mg, 57%). 1H NMR (400 MHz, CDCl3) delta7.20, 7.10, 6.61, 4.22, 4.01, 3.85, 1.7, 1.6, 1.06.

Reference： [1]Patent: US2003/130305,2003,A1

14
[ 7758-89-6 ]
[ 5035-82-5 ]
[ 107-21-1 ]
[ 192863-64-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide; sodium nitrite; In 1,4-dioxane; dichloromethane; ethyl acetate;	PREPARATION 20 2-chloro-3,4,5-trimethoxybenzoic Acid Combine methyl 2-amino-3,4,5-trimethoxybenzoate (4.8 g, 20 mmol) and dichloromethane (20 mL). Cool in an ice bath. Add a solution of hydrochloric acid in dioxane (10 mL, 4 M, 40 mmol). Add polyethylene glycol 200 (20 mL): followed by sodium nitrite (2.76 g, 40 mmol). After 10 minutes add copper (I) chloride (3.96 g, 40 mmol). Warm to ambient temperature. After 18 hours, dilute the reaction mixture with ethyl acetate and extract with a 1 M aqueous solution of sodium hydroxide an then brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. the title compound. Chromatograph the residue on silica gel eluding sequentially with hexane and then 5% ethyl acetate/hexane to give methyl 2-chloro-3,4,5-trimethoxybenzoate: Rf=0.7 (silica gel, 20% ethyl acetate/toluene).
	With hydrogenchloride; sodium hydroxide; sodium nitrite; In 1,4-dioxane; dichloromethane; ethyl acetate;	PREPARATION 20 2-chloro-3,4,5-trimethoxybenzoic acid Combine methyl 2-amino-3,4,5-trimethoxybenzoate (4.8 g, 20 mmol) and dichloromethane (20 mL). Cool in an ice bath. Add a solution of hydrochloric acid in dioxane (10 mL, 4 M, 40 mmol). Add polyethylene glycol 200 (20 mL) followed by sodium nitrite (2.76 g, 40 mmol). After 10 minutes add copper (I) chloride (3.96 g, 40 mmol). Warm to ambient temperature. After 18 hours, dilute the reaction mixture with ethyl acetate and extract with a 1 M aqueous solution of sodium hydroxide an then brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. the title compound. Chromatograph the residue on silica gel eluding sequentially with hexane and then 5% ethyl acetate/hexane to give methyl 2-chloro-3,4,5-trimethoxybenzoate: Rf=0.7 (silica gel, 20% ethyl acetate/toluene).

Reference： [1]Patent: US2001/34343,2001,A1
[2]Patent: US6423704,2002,B1

15
[ 7758-89-6 ]
[ 371970-02-4 ]
1-{3-[5-Acetyl-2-(4-Chlorophenyl)-1-Methyl-1H-Indol-3-yl]-1-Oxopropyl}-4-(Phenylmethyl)-4-Piperidinol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	palladium(II) chloride; In dimethylformamide-water;	EXAMPLE 50 1-{3-[5-Acetyl-2-(4-Chlorophenyl)-1-Methyl-1H-Indol-3-yl]-1-Oxopropyl}-4-(Phenylmethyl)-4-Piperidinol A mixture of palladium chloride (2 mg, 0.012 mmol) and copper (I) chloride (12 mg, 0.12 mmol) in dimethylformamide-water (7:1, 11 mL) was stirred under oxygen at room temperature for 1 h. A solution of 1-{3- [2-(4-chlorophenyl)-5-ethenyl-1-methyl-1H-indol-3-yl] -1-oxopropyl}-4-(phenylmethyl)-4-piperidinol (Example 44, 60 mg, 0.12 mmol) in dimethylformamide-water (7:1, 5 mL) was added dropwise over 5 min. and the mixture was stirred under oxygen at room temperature for 24 h. The mixture was poured into hydrochloric acid (2M, 100 mL) and extracted with ether (5*30 mL). The combined organic fractions were washed with aqueous sodium hydrogen carbonate (saturated, 30 mL) and brine (30 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluding with ethyl acetate: hexane (1:1), to give the title compound. 1H NMR (360 MHz, CDCl3) delta8.32 (1H, d, J 1.6 Hz), 7.94 (1H, dd, J 8.6, 1.6 Hz), 7.51-7.47 (2H, m), 7.36-7.24 (7H, m), 7.14 (1H, d, J 8.6 Hz), 4.34 (1H, br d, J 12.9 Hz), 3.59 (3H, s), 3.37 (1H, br d, J 13.4 Hz), 3.18 (1H, dt, Jt 12.5, Jd 2.9 Hz), 3.12-3.05 (2H, m), 2.90-2.82 (1H, m), 2.69 (3H, s), 2.66 (2H, s), 2.55-2.50 (2H, m), and 1.45-1.19 (4H, m). m/z (ES+) 529, 531 (M+1).

Reference： [1]Patent: US2001/39286,2001,A1

16
[ 7758-89-6 ]
[ 344420-53-7 ]
[ 1634-04-4 ]
methyl [2-(5-acetylamino-2-chloro-4-fluorophenoxy)phenoxy]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium nitrite; In water;	Fifth Process: To 30 ml of conc. hydrochloric acid was added 2.0 g of methyl [2-(5-acetylamino-2-amino-4-fluorophenoxy)phenoxy]acetate, and the mixture was stirred for 1 hour at room temperature. Thereafter, a mixture of 0.42 g of sodium nitrite and 3 ml of water was added under ice cool. The mixture was stirred for 1 hour under the same condition, then, 40 ml of t-butyl methyl ether was added, then, 0.85 g of copper (I) chloride was added. The mixture was stirred for 30 minutes, then, water was added to this, and extracted with t-butyl methyl ether, and the organic layer was washed with water, dried over magnesium sulfate and concentrated, and the resulted residue was purified by column chromatography (eluent: hexane/ethyl acetate=2/1) to obtain 0.52 g of methyl [2-(5-acetylamino-2-chloro-4-fluorophenoxy)phenoxy]acetate. Melting Point: 138.9 C.