Name: 42471-59-0|1-Bromo-3-(methoxymethoxy)benzene|98%
Brand: Ambeed
SKU: A281729
Price: 14.0 USD
Availability: InStock
Rating: 99 (35 reviews)

1
[ 59397-48-7 ]
[ 42471-59-0 ]
[ 127973-01-7 ]

Yield	Reaction Conditions	Operation in experiment
	With magnesium 1.) THF, 4 h, 2.) 10 h; Multistep reaction;

Reference： [1]Thurkauf, Andrew; Costa, Brian de; Mattson, Mariena V.; France, Charles P.; Price, Madelon T.; et al. [Journal of Medicinal Chemistry, 1990, vol. 33, # 8, p. 2211 - 2215]

2
[ 431-47-0 ]
[ 42471-59-0 ]
[ 113787-80-7 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h; Yield given. Multistep reaction;

Reference： [1]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

3
[ 42471-59-0 ]
[ 15448-47-2 ]
[ 138691-29-9 ]

Yield	Reaction Conditions	Operation in experiment
	With dimethylsulfide; magnesium; copper(I) bromide 2.) THF, -15 deg C; Yield given. Multistep reaction;

Reference： [1]Napolitano, Elio [Gazzetta Chimica Italiana, 1991, vol. 121, # 9, p. 455 - 456]

4
[ 591-20-8 ]
[ 107-30-2 ]
[ 42471-59-0 ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: 3-Bromophenol With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; Stage #2: chloromethyl methyl ether In N,N-dimethyl-formamide at 0 - 20℃; Further stages.;
96%	With potassium carbonate In acetone for 18h; Heating;
95%	Stage #1: 3-Bromophenol With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 2.67h; Stage #2: chloromethyl methyl ether In N,N-dimethyl-formamide at 0 - 20℃;

94%	With potassium carbonate In acetone for 16h; Reflux;
91%	Stage #1: 3-Bromophenol With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: chloromethyl methyl ether In N,N-dimethyl-formamide; mineral oil at 20℃; for 6h;	Phenol fragment 5.¹ To a stirred solution of m-bromophenol8 (1.46 g, 8.44 mmol) in DMF (10 ml) was added NaH (60% in oil, 440 mg, 11.0 mmol) at 0° C. After being stirred for 30 min, a solution of MOMCl (0.84 ml, 11.0 mmol) in DMF (4.0 ml) was added. The reaction mixture was stirred at room temperature for additional 6 h. The reaction mixture was quenched with saturated aqueous NH4Cl, and extracted with EtO. The organic layer was washed with brine, dried over Na2S04 and concentrated. Purification of the residue by flash column chromatography (hexane/EtOAc = 10/1) gave 51 (1.66 g, 7.65 mmol) in 91% yield.
89%	With N-ethyl-N,N-diisopropylamine In dichloromethane
88%	With sodium hydride In N,N-dimethyl-formamide at 20℃; for 2h;
51%	Stage #1: 3-Bromophenol With potassium carbonate In acetone at 20℃; Inert atmosphere; Schlenk technique; Stage #2: chloromethyl methyl ether In acetone at 60℃; for 16h; Inert atmosphere; Schlenk technique;
	With sodium hydride Yield given. Multistep reaction;
	With potassium hydroxide 1.) methanol, 2.) acetonitrile, RT, 30 min; Yield given. Multistep reaction;
	With sodium hydride In N,N-dimethyl-formamide at 0℃;
		18.a 3-Methoxymethoxy-2'-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1';4',1"]terphenyl-4"-carboxylic Acid (a) 3-Methoxymethoxybromobenzene. In a manner similar to that of Example 7(a), by reaction of 100.00 g (577.9 mmol) of 3-bromophenol with 48.28 g (635.8 mmol) of chloromethyl methyl ether, 135.32 g (100%) of the expected product are obtained in the form of a pale beige oil. 1H NMR (CDCl3) δ 3.46 (s, 3H), 5.15 (s, 2H), 6.92 to 7.00 (m, 1H), 7.10 to 7.14 (m, 2H), 7.18 to 7.22 (m, 1H).
		29.a (a) (a) 3-Methoxymethoxybromobenzene: In a similar manner to that of Example 28(a), starting with 48.84 g (282.3 mmol) of 3-bromophenol and 25.00 g (310.5 mmol) of methyl chloromethyl ether, 65.00 g (100%) of the expected compound are obtained in the form of a yellow oil. 1 H NMR (CDCl3) δ 3.48 (s, 3H), 5.15 (s, 2H), 6.92 to 7.00 (m, 2H), 7.10 to 7.18 (m, 4H), 7.18 to 7.22 (m, 2H).
	With N-ethyl-N,N-diisopropylamine In dichloromethane	1.2 Preparation of 4-[(3-(naphth-2-yl)methoxyphen-1-yl)hydroxymethyl]tetrahydropyran. Step 2. 3-methyloxymethoxy-bromobenzene. To a solution of 3-bromophenol (27.4 g, 158 mmol) in CH2 Cl2 was added chloromethyl methyl ether (18 mL, 237 mmol). The reaction mixture was cooled to 0° C. and diisopropylethylamine (55 mL, 316 mmol) was added and the cold bath was removed. The reaction mixture was stirred for 3 hours at ambient temperature and then poured into 10% aqueous HCl. The layers were separated and the aqueous phase was extracted 4 times with CH2 Cl2. The combined organic layers were washed once each with saturated aqueous NaHCO3, 15% aqueous NaOH, and brine, dried over MgSO4, filtered, and concentrated in vacuo to provide 3-methyloxymethoxy-bromobenzene as a yellow oil.
	With N-ethyl-N,N-diisopropylamine In dichloromethane	3.1 Preparation of E- and Z-O-Methyl-4-[(3-(4-N-acetyl-N-methylamino)benzyloxy)phenyl)oximinomethyl]tetrahydropyran. Step 1. 3-(methyloxymethoxy)bromobenzene. To a solution of 3-bromophenol (27.4 g, 158 mmol) in CH2 Cl2 was added chloromethyl methyl ether (18 mL, 237 mmol). The reaction mixture was cooled to 0° C. and diisopropylethylamine (55 mL, 316 mmol) was added and the cold bath was removed. The reaction mixture was stirred for 3 hours at ambient temperature and then poured into 10% aqueous HCl. The layers were separated and the aqueous phase was extracted 4 times with CH2 Cl2. The combined organic layers were washed once each with saturated aqueous NaHCO3, 15% aqueous NaOH, and brine, dried over MGSO4, filtered, and concentrated in vacuo to provide 3-methyloxymethoxybromobenzene as a yellow oil.
	Stage #1: 3-Bromophenol With sodium hydroxide In DMF (N,N-dimethyl-formamide) at 20℃; for 0.5h; Stage #2: chloromethyl methyl ether In DMF (N,N-dimethyl-formamide) at 20℃; for 0.5h;	1 1-bromo-3-(methoxymethoxy)benzene: Reference Example 1 1-bromo-3-(methoxymethoxy)benzene: Sodium hydroxide (24.2g) was washed with hexane, and then was added by N,N-dimethylformamide (500mL; DMF) and the mixture was cooled down, dropped by 3-bromophenol (99.6g) and stirred for 30 minutes at a room temperature. The mixture was cooled down, dropped by chloromethylether (46mL) and stirred for 30 minutes at a room temperature. The mixture was poured into iced water (2000mL) and extracted by mixed solvent (hexane: ethyl acetate = 2: 1). The extract was washed with water and saturated brine successively, dried over anhydrous magnesium sulfate and then concentrated to give the title compound (32.6g) having the following physical data. TLC: Rf 0.80 (hexane: ethyl acetate = 2: 1).
	With N-ethyl-N,N-diisopropylamine In dichloromethane at -78 - 20℃;	1 To a solution of 3-bromophenol (10 g, 57.8 mmol) and Hunig's base (35.7 mL, 205 mmol) in CH2Cl2 (30 mL) at -78 0C, was added MOM-Cl (10.98 mL, 145 mmol). The mixture was warmed to room temperature and stirred overnight. The mixture was diluted with water (150 mL), stirred for 15 min and extracted with CH2Cl2 (2x). The CH2Cl2 extract was washed with brine, dried (Na2SO4), filtered and concentrated to give a yellow oil. The material was purified by column chromatography on SiO2 (gradient from 0 to 20% EtOAc/hexanes) to give the title compound as a colorless oil.

Reference： [1]Kaiser, Florian; Schwink, Lothar; Velder, Janna; Schmalz, Hans-Guenther [Journal of Organic Chemistry, 2002, vol. 67, # 26, p. 9248 - 9256]
[2]Uchiyama, Masanobu; Kobayashi, Yuri; Furuyama, Taniyuki; Nakamura, Shinji; Kajihara, Yumiko; Miyoshi, Tomoko; Sakamoto, Takao; Kondo, Yoshinori; Morokuma, Keiji [Journal of the American Chemical Society, 2008, vol. 130, # 2, p. 472 - 480]
[3]Neufeind, Stefan; Huelsken, Nils; Neudoerfl, Joerg-Martin; Schloerer, Nils; Schmalz, Hans-Guenther [Chemistry - A European Journal, 2011, vol. 17, # 9, p. 2633 - 2641]
[4]Youn, So Won; Kim, Young Ho; Jo, Yoon Hyung [Advanced Synthesis and Catalysis, 2019, vol. 361, # 3, p. 462 - 468]
[5]Yoshino, Tatsuya; Yamashita, Shuji; Sato, Itaru; Hayashi, Yujiro; Hirama, Masahiro [Chemistry Letters, 2014, vol. 43, # 3, p. 349 - 351]
[6]Cetin, Sultan; Elmazoglu, Zubeyir; Karaman, Osman; Gunduz, Hande; Gunbas, Gorkem; Kolemen, Safacan [ACS Medicinal Chemistry Letters, 2021, vol. 12, # 5, p. 752 - 757]
[7]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]
[8]Doering, Nicolle A.; Kou, Kevin G. M.; Norseeda, Krissada; Lee, Jack C.; Marth, Christopher J.; Gallego, Gary M.; Sarpong, Richmond [Journal of Organic Chemistry, 2018, vol. 83, # 20, p. 12911 - 12920]
[9]Napolitano, Elio [Gazzetta Chimica Italiana, 1991, vol. 121, # 9, p. 455 - 456]
[10]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]
[11]Richardson, Timothy I.; Norman, Bryan H.; Lugar, Charles W.; Jones, Scott A.; Wang, Yong; Durbin, Jim D.; Krishnan, Venkatesh; Dodge, Jeffrey A. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3570 - 3574]
[12]Current Patent Assignee: Eqt Partners AB; Galderma (in: EQT Partners) - US6316009, 2001, B1
[13]Current Patent Assignee: Eqt Partners AB; Galderma (in: EQT Partners) - US6150413, 2000, A
[14]Current Patent Assignee: ABBOTT LABORATORIES INC - US5354865, 1994, A
[15]Current Patent Assignee: ABBOTT LABORATORIES INC - US5484786, 1996, A
[16]Current Patent Assignee: ONO PHARMACEUTICAL CO LTD - EP1604971, 2005, A1 Location in patent: Page/Page column 19
[17]Current Patent Assignee: MERCK & CO INC - WO2010/94120, 2010, A1 Location in patent: Page/Page column 67

5
[ 340-07-8 ]
[ 42471-59-0 ]
[ 113787-80-7 ]

Yield	Reaction Conditions	Operation in experiment
	With magnesium 1.) THF, 2.) THF, 0 deg C; Yield given. Multistep reaction;

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]

6
[ 42471-59-0 ]
[ 179261-00-8 ]
(R)-2-(3-Methoxymethoxy-phenyl)-1-(4-methoxy-3-triisopropylsilanyloxy-phenyl)-ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium 1.) THF, hexane, 1 h, 2.) THF, hexane, 12 h; Yield given. Multistep reaction;

Reference： [1]Ramacciotti, Alessio; Fiaschi, Rita; Napolitano, Elio [Journal of Organic Chemistry, 1996, vol. 61, # 16, p. 5371 - 5374]

Yield	Reaction Conditions	Operation in experiment
	3-Bromphenol, NaH, Chlormethyl-methylether;
	Bromphenol, NaH/n-C6H14, Chloromethylmethylaether <1018/19>;

8
[ 42471-59-0 ]
[ 118794-69-7 ]
[ 491607-99-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: 1-bromo-3-(methoxymethoxy)benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #2: With cerium(III) chloride In tetrahydrofuran; hexane at -78℃; for 1h; Stage #3: 6-[(tert-butyldimethylsilyl)oxy]hexanal In tetrahydrofuran; hexane at -78 - 20℃; Further stages.;

Reference： [1]Kaiser, Florian; Schwink, Lothar; Velder, Janna; Schmalz, Hans-Guenther [Journal of Organic Chemistry, 2002, vol. 67, # 26, p. 9248 - 9256]

9
[ 364629-88-9 ]
[ 42471-59-0 ]
[ 239067-67-5 ]

Yield	Reaction Conditions	Operation in experiment
59%	Stage #1: 1-bromo-3-(methoxymethoxy)benzene With magnesium In tetrahydrofuran for 0.5h; Heating; Stage #2: 5-(4-chloro-phenoxy)-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1<i>H</i>-6-oxa-1-aza-chrysene In tetrahydrofuran; toluene at 20℃; for 12h; Further stages.;

Reference： [1]Coghlan; Kym; Elmore; Wang; Luly; Wilcox; Stashko; Lin; Miner; Tyree; Jacobson; Nakane; Lane [Journal of Medicinal Chemistry, 2001, vol. 44, # 18, p. 2879 - 2885]

10
[ 42471-59-0 ]
[ 17997-47-6 ]
[ 862743-02-0 ]

Reference： [1]Kalyani, Dipannita; Sanford, Melanie S. [Organic Letters, 2005, vol. 7, # 19, p. 4149 - 4152]

11
(1SR,2RS)-2-(2,5-bis-methoxymethoxyphenyl)cyclopentanecarboxylic acid methoxymethylamide [ No CAS ]
[ 42471-59-0 ]
C₂₄H₃₀O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-bromo-3-(methoxymethoxy)benzene With tert.-butyl lithium In tetrahydrofuran at -78℃; Stage #2: (1SR,2RS)-2-(2,5-bis-methoxymethoxyphenyl)cyclopentanecarboxylic acid methoxymethylamide In tetrahydrofuran at -78℃; Further stages.;

Reference： [1]Richardson, Timothy I.; Norman, Bryan H.; Lugar, Charles W.; Jones, Scott A.; Wang, Yong; Durbin, Jim D.; Krishnan, Venkatesh; Dodge, Jeffrey A. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3570 - 3574]

12
[ 42471-59-0 ]
C₁₈H₁₈O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: t-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: p-TsOH / methanol / 50 °C

Reference： [1]Richardson, Timothy I.; Norman, Bryan H.; Lugar, Charles W.; Jones, Scott A.; Wang, Yong; Durbin, Jim D.; Krishnan, Venkatesh; Dodge, Jeffrey A. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3570 - 3574]

13
[ 42471-59-0 ]
C₁₈H₁₈O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: t-BuLi / tetrahydrofuran / -78 °C 1.2: tetrahydrofuran / -78 °C 2.1: p-TsOH / methanol / 50 °C 3.1: Na(CN)BH₃; HCl / 20 °C

Reference： [1]Richardson, Timothy I.; Norman, Bryan H.; Lugar, Charles W.; Jones, Scott A.; Wang, Yong; Durbin, Jim D.; Krishnan, Venkatesh; Dodge, Jeffrey A. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 13, p. 3570 - 3574]

14
[ 42471-59-0 ]
4-methoxymethoxy-2-pyridin-2-yl-phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 76 percent / Pd(OAc)2 / benzene / 1 h / 100 °C 2: 41 percent / K₂CO₃ / methanol / 12 h

Reference： [1]Kalyani, Dipannita; Sanford, Melanie S. [Organic Letters, 2005, vol. 7, # 19, p. 4149 - 4152]

15
[ 42471-59-0 ]
[ 862743-03-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 76 percent / Pd(OAc)2 / benzene / 1 h / 100 °C

Reference： [1]Kalyani, Dipannita; Sanford, Melanie S. [Organic Letters, 2005, vol. 7, # 19, p. 4149 - 4152]

16
[ 42471-59-0 ]
[ 491608-02-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: n-BuLi / tetrahydrofuran; hexane / 0.25 h / -78 °C 1.2: cerium(III) chloride / tetrahydrofuran; hexane / 1 h / -78 °C 1.3: 86 percent / tetrahydrofuran; hexane / -78 - 20 °C 2.1: n-BuLi / toluene; hexane; tetrahydrofuran / 4.5 h / -43 - 20 °C 2.2: 83 percent / tetrafluorodibromoethane / hexane; toluene; tetrahydrofuran / -43 - 20 °C

Reference： [1]Kaiser, Florian; Schwink, Lothar; Velder, Janna; Schmalz, Hans-Guenther [Journal of Organic Chemistry, 2002, vol. 67, # 26, p. 9248 - 9256]

17
[ 42471-59-0 ]
2-bromo-1-[6-(tert-butyldimethylsilanyloxy)-1-triethylsilanyloxyhexyl]-3-methoxymethoxybenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: n-BuLi / tetrahydrofuran; hexane / 0.25 h / -78 °C 1.2: cerium(III) chloride / tetrahydrofuran; hexane / 1 h / -78 °C 1.3: 86 percent / tetrahydrofuran; hexane / -78 - 20 °C 2.1: n-BuLi / toluene; hexane; tetrahydrofuran / 4.5 h / -43 - 20 °C 2.2: 83 percent / tetrafluorodibromoethane / hexane; toluene; tetrahydrofuran / -43 - 20 °C 3.1: 93 percent / imidazole; DMAP / CH₂Cl₂ / 8 h / 20 °C

Reference： [1]Kaiser, Florian; Schwink, Lothar; Velder, Janna; Schmalz, Hans-Guenther [Journal of Organic Chemistry, 2002, vol. 67, # 26, p. 9248 - 9256]

18
[ 42471-59-0 ]
6-[3-hydroxy-2-(3-hydroxy-8-methoxy-9,10-anthraquinone-1-carbonyl)phenyl]-6-oxohexanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: n-BuLi / tetrahydrofuran; hexane / 0.25 h / -78 °C 1.2: cerium(III) chloride / tetrahydrofuran; hexane / 1 h / -78 °C 1.3: 86 percent / tetrahydrofuran; hexane / -78 - 20 °C 2.1: n-BuLi / toluene; hexane; tetrahydrofuran / 4.5 h / -43 - 20 °C 2.2: 83 percent / tetrafluorodibromoethane / hexane; toluene; tetrahydrofuran / -43 - 20 °C 3.1: n-BuLi / hexane; tetrahydrofuran / 0.5 h / -78 °C 3.2: 52 percent / hexane; tetrahydrofuran / -78 - 20 °C 4.1: Jones reagent / acetone / 3 h / 20 °C 4.2: 40 mg / molecular sieves 4 Angstroem; trimethylsilyliodide / CH₂Cl₂; acetonitrile / -30 - 0 °C

Reference： [1]Kaiser, Florian; Schwink, Lothar; Velder, Janna; Schmalz, Hans-Guenther [Journal of Organic Chemistry, 2002, vol. 67, # 26, p. 9248 - 9256]

19
[ 42471-59-0 ]
6-[3-methoxymethoxy-2-(8-methoxy-3-methoxymethoxy-9,10-anthraquinone-1-carbonyl)-phenyl]-6-oxo-hexanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: n-BuLi / tetrahydrofuran; hexane / 0.25 h / -78 °C 1.2: cerium(III) chloride / tetrahydrofuran; hexane / 1 h / -78 °C 1.3: 86 percent / tetrahydrofuran; hexane / -78 - 20 °C 2.1: n-BuLi / toluene; hexane; tetrahydrofuran / 4.5 h / -43 - 20 °C 2.2: 83 percent / tetrafluorodibromoethane / hexane; toluene; tetrahydrofuran / -43 - 20 °C 3.1: n-BuLi / hexane; tetrahydrofuran / 0.5 h / -78 °C 3.2: 52 percent / hexane; tetrahydrofuran / -78 - 20 °C 4.1: Jones reagent / acetone / 3 h / 20 °C

Reference： [1]Kaiser, Florian; Schwink, Lothar; Velder, Janna; Schmalz, Hans-Guenther [Journal of Organic Chemistry, 2002, vol. 67, # 26, p. 9248 - 9256]

20
[ 42471-59-0 ]
[ 491607-76-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: n-BuLi / tetrahydrofuran; hexane / 0.25 h / -78 °C 1.2: cerium(III) chloride / tetrahydrofuran; hexane / 1 h / -78 °C 1.3: 86 percent / tetrahydrofuran; hexane / -78 - 20 °C 2.1: n-BuLi / toluene; hexane; tetrahydrofuran / 4.5 h / -43 - 20 °C 2.2: 83 percent / tetrafluorodibromoethane / hexane; toluene; tetrahydrofuran / -43 - 20 °C 3.1: n-BuLi / hexane; tetrahydrofuran / 0.5 h / -78 °C 3.2: 52 percent / hexane; tetrahydrofuran / -78 - 20 °C

Reference： [1]Kaiser, Florian; Schwink, Lothar; Velder, Janna; Schmalz, Hans-Guenther [Journal of Organic Chemistry, 2002, vol. 67, # 26, p. 9248 - 9256]

21
[ 42471-59-0 ]
[ 113787-85-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature 4: NH₃ (liq.) / CH₂Cl₂ / 12 h / Ambient temperature 5: 79 percent / tert-butyl hypochlorite, Et₃N / 2-methyl-propan-2-ol; ethanol / 0.5 h / 0 °C 6: acetic acid, 1N aq. HCl / 12 h / Ambient temperature
	Multi-step reaction with 6 steps 1: 1) BuLi, / 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h 2: 99 percent / hydroxylamine hydrochloride / pyridine; ethanol / 4 h / Heating 3: 85 percent / pyridine / 2 h / Heating 4: 73 percent / NH₃ / diethyl ether / 8 h / -78 °C 5: Ag₂O / diethyl ether / 3 h / in the dark 6: 54 percent / glacial acetic acid, 2M HCl / 3 h / in the dark

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]
[2]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

22
[ 42471-59-0 ]
[ 113787-84-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature 4: NH₃ (liq.) / CH₂Cl₂ / 12 h / Ambient temperature 5: 79 percent / tert-butyl hypochlorite, Et₃N / 2-methyl-propan-2-ol; ethanol / 0.5 h / 0 °C
	Multi-step reaction with 5 steps 1: 1) BuLi, / 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h 2: 99 percent / hydroxylamine hydrochloride / pyridine; ethanol / 4 h / Heating 3: 85 percent / pyridine / 2 h / Heating 4: 73 percent / NH₃ / diethyl ether / 8 h / -78 °C 5: Ag₂O / diethyl ether / 3 h / in the dark

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]
[2]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

23
[ 42471-59-0 ]
[ 113787-83-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature 4: NH₃ (liq.) / CH₂Cl₂ / 12 h / Ambient temperature
	Multi-step reaction with 4 steps 1: 1) BuLi, / 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h 2: 99 percent / hydroxylamine hydrochloride / pyridine; ethanol / 4 h / Heating 3: 85 percent / pyridine / 2 h / Heating 4: 73 percent / NH₃ / diethyl ether / 8 h / -78 °C

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]
[2]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

24
[ 42471-59-0 ]
[ 113787-82-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature
	Multi-step reaction with 3 steps 1: 1) BuLi, / 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h 2: 99 percent / hydroxylamine hydrochloride / pyridine; ethanol / 4 h / Heating 3: 85 percent / pyridine / 2 h / Heating

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]
[2]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

25
[ 42471-59-0 ]
[ 113787-81-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C
	Multi-step reaction with 2 steps 1: 1) BuLi, / 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h 2: 99 percent / hydroxylamine hydrochloride / pyridine; ethanol / 4 h / Heating

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]
[2]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

26
[ 42471-59-0 ]
[ 152565-40-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature 4: NH₃ (liq.) / CH₂Cl₂ / 12 h / Ambient temperature 5: 79 percent / tert-butyl hypochlorite, Et₃N / 2-methyl-propan-2-ol; ethanol / 0.5 h / 0 °C 6: acetic acid, 1N aq. HCl / 12 h / Ambient temperature 7: K₂CO₃, 18-crown-6 / tetrahydrofuran / 18 h / Ambient temperature

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]

27
[ 42471-59-0 ]
[ 156824-43-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature 4: NH₃ (liq.) / CH₂Cl₂ / 12 h / Ambient temperature 5: 79 percent / tert-butyl hypochlorite, Et₃N / 2-methyl-propan-2-ol; ethanol / 0.5 h / 0 °C 6: acetic acid, 1N aq. HCl / 12 h / Ambient temperature 7: K₂CO₃, 18-crown-6 / tetrahydrofuran / 18 h / Ambient temperature 8: 75 percent / nitric acid, acetic anhydride / 0.5 h / Ambient temperature

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]

28
[ 42471-59-0 ]
3,4-dihydro-7-<3-(trifluoromethyl)-3H-diazirin-3-yl>-2H-1,4-benzoxazin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature 4: NH₃ (liq.) / CH₂Cl₂ / 12 h / Ambient temperature 5: 79 percent / tert-butyl hypochlorite, Et₃N / 2-methyl-propan-2-ol; ethanol / 0.5 h / 0 °C 6: acetic acid, 1N aq. HCl / 12 h / Ambient temperature 7: K₂CO₃, 18-crown-6 / tetrahydrofuran / 18 h / Ambient temperature 8: 75 percent / nitric acid, acetic anhydride / 0.5 h / Ambient temperature 9: 1.) sodium hydrosulfite, 0.1N NaOH, 2.) N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline / 1.) water, RT, 30 min, 2.) water, ether, RT, 30 min

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]

29
[ 42471-59-0 ]
<3-(2,2,2-trifluoro-1-methoxyethyl)phenoxy>acetic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature 4: NH₃ (liq.) / CH₂Cl₂ / 12 h / Ambient temperature 5: 79 percent / tert-butyl hypochlorite, Et₃N / 2-methyl-propan-2-ol; ethanol / 0.5 h / 0 °C 6: acetic acid, 1N aq. HCl / 12 h / Ambient temperature 7: K₂CO₃, 18-crown-6 / tetrahydrofuran / 18 h / Ambient temperature 8: 74 percent / 24 h / Irradiation

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]

30
[ 42471-59-0 ]
[ 156824-44-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature 4: NH₃ (liq.) / CH₂Cl₂ / 12 h / Ambient temperature 5: 79 percent / tert-butyl hypochlorite, Et₃N / 2-methyl-propan-2-ol; ethanol / 0.5 h / 0 °C 6: acetic acid, 1N aq. HCl / 12 h / Ambient temperature 7: K₂CO₃, 18-crown-6 / tetrahydrofuran / 18 h / Ambient temperature 8: 75 percent / nitric acid, acetic anhydride / 0.5 h / Ambient temperature 9: 93 percent / 1N aq. NaOH / methanol / 0.5 h / Ambient temperature

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]

31
[ 42471-59-0 ]
<2-nitro-5-(2,2,2-trifluoro-1-methoxyethyl)phenoxy>acetic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature 4: NH₃ (liq.) / CH₂Cl₂ / 12 h / Ambient temperature 5: 79 percent / tert-butyl hypochlorite, Et₃N / 2-methyl-propan-2-ol; ethanol / 0.5 h / 0 °C 6: acetic acid, 1N aq. HCl / 12 h / Ambient temperature 7: K₂CO₃, 18-crown-6 / tetrahydrofuran / 18 h / Ambient temperature 8: 75 percent / nitric acid, acetic anhydride / 0.5 h / Ambient temperature 9: 34 percent / 12 h / Irradiation

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]

32
[ 42471-59-0 ]
1-<<<2-nitro-5-<3-(trifluoromethyl)-3H-diazirin-3-yl>phenoxy>acetyl>oxy>-2,5-pyrrolidinedione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1: 1.) Mg / 1.) THF, 2.) THF, 0 deg C 2: 99 percent / NH₂OH*HCl / ethanol; pyridine / 4 h / 60 °C 3: Et₃N, N,N-dimethylaminopyridine / CH₂Cl₂ / 0.5 h / Ambient temperature 4: NH₃ (liq.) / CH₂Cl₂ / 12 h / Ambient temperature 5: 79 percent / tert-butyl hypochlorite, Et₃N / 2-methyl-propan-2-ol; ethanol / 0.5 h / 0 °C 6: acetic acid, 1N aq. HCl / 12 h / Ambient temperature 7: K₂CO₃, 18-crown-6 / tetrahydrofuran / 18 h / Ambient temperature 8: 75 percent / nitric acid, acetic anhydride / 0.5 h / Ambient temperature 9: 93 percent / 1N aq. NaOH / methanol / 0.5 h / Ambient temperature 10: 93 percent / DCC / CH₂Cl₂ / 0.5 h / Ambient temperature

Reference： [1]Hatanaka; Hashimoto; Nakayama; Kanaoka [Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 4, p. 826 - 831]

33
[ 42471-59-0 ]
[ 113787-78-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 1) BuLi, / 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h 2: 99 percent / hydroxylamine hydrochloride / pyridine; ethanol / 4 h / Heating 3: 85 percent / pyridine / 2 h / Heating 4: 73 percent / NH₃ / diethyl ether / 8 h / -78 °C 5: Ag₂O / diethyl ether / 3 h / in the dark 6: 54 percent / glacial acetic acid, 2M HCl / 3 h / in the dark 7: 95 percent / potassium carbonate / acetone / in the dark 8: 16 percent / trifluoroacetic acid, anisole / 0.25 h / Heating

Reference： [1]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

34
[ 42471-59-0 ]
[ 113787-92-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1: 1) BuLi, / 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h 2: 99 percent / hydroxylamine hydrochloride / pyridine; ethanol / 4 h / Heating 3: 85 percent / pyridine / 2 h / Heating 4: 73 percent / NH₃ / diethyl ether / 8 h / -78 °C 5: Ag₂O / diethyl ether / 3 h / in the dark 6: 54 percent / glacial acetic acid, 2M HCl / 3 h / in the dark 7: 100 percent / potassium carbonate / acetone / Ambient temperature; protection from light 8: 65 percent / trifluoroacetic acid, anisole / 20 °C 9: 77 percent / methanol; CHCl₃ / 2 h / 0 °C

Reference： [1]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

35
[ 42471-59-0 ]
[ 113787-91-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 1) BuLi, / 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h 2: 99 percent / hydroxylamine hydrochloride / pyridine; ethanol / 4 h / Heating 3: 85 percent / pyridine / 2 h / Heating 4: 73 percent / NH₃ / diethyl ether / 8 h / -78 °C 5: Ag₂O / diethyl ether / 3 h / in the dark 6: 54 percent / glacial acetic acid, 2M HCl / 3 h / in the dark 7: 100 percent / potassium carbonate / acetone / Ambient temperature; protection from light 8: 65 percent / trifluoroacetic acid, anisole / 20 °C

Reference： [1]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

36
[ 42471-59-0 ]
[ 113787-86-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 1) BuLi, / 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h 2: 99 percent / hydroxylamine hydrochloride / pyridine; ethanol / 4 h / Heating 3: 85 percent / pyridine / 2 h / Heating 4: 73 percent / NH₃ / diethyl ether / 8 h / -78 °C 5: Ag₂O / diethyl ether / 3 h / in the dark 6: 54 percent / glacial acetic acid, 2M HCl / 3 h / in the dark 7: 95 percent / potassium carbonate / acetone / in the dark

Reference： [1]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

37
[ 42471-59-0 ]
[ 113787-90-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: 1) BuLi, / 1) THF, -78 deg C, 1h, 2) THF, -78 deg C, 1h 2: 99 percent / hydroxylamine hydrochloride / pyridine; ethanol / 4 h / Heating 3: 85 percent / pyridine / 2 h / Heating 4: 73 percent / NH₃ / diethyl ether / 8 h / -78 °C 5: Ag₂O / diethyl ether / 3 h / in the dark 6: 54 percent / glacial acetic acid, 2M HCl / 3 h / in the dark 7: 100 percent / potassium carbonate / acetone / Ambient temperature; protection from light

Reference： [1]Baldwin; Pratt; Moloney [Tetrahedron, 1987, vol. 43, # 11, p. 2565 - 2575]

38
[ 42471-59-0 ]
[ 138691-30-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) Mg, 2.) CuBr, dimethyl sulphide / 2.) THF, -15 deg C 2: NaH / diethyl ether

Reference： [1]Napolitano, Elio [Gazzetta Chimica Italiana, 1991, vol. 121, # 9, p. 455 - 456]

39
[ 42471-59-0 ]
(R)-(-)-mellein [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) Mg, 2.) CuBr, dimethyl sulphide / 2.) THF, -15 deg C
	Multi-step reaction with 3 steps 1: 1.) Mg, 2.) CuBr, dimethyl sulphide / 2.) THF, -15 deg C 2: NaH / diethyl ether

Reference： [1]Napolitano, Elio [Gazzetta Chimica Italiana, 1991, vol. 121, # 9, p. 455 - 456]
[2]Napolitano, Elio [Gazzetta Chimica Italiana, 1991, vol. 121, # 9, p. 455 - 456]

40
30o [ No CAS ]
[ 35394-09-3 ]
[ 42471-59-0 ]
1-hydroxy-2-methoxy-1-(3-methoxymethoxyphenyl)cyclopentane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With magnesium In tetrahydrofuran; dichloromethane	1 Example 1 A Grignard reagent was prepared by heating a mixture of 3-methoxymethoxyphenyl bromide (5 g), magnesium (0.55 g) and tetrahydrofuran (20 ml) to 30o for 2 hours. The reagent was cooled to ambient temperature and a solution of 2-methoxycyclopentanone (2.5 g; Bull. Soc. Chim. France , 1973, 1417) in tetrahydrofuran (8 ml) was added dropwise. The mixture was stirred at ambient temperature for 15 hours and evaporated. The residue was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous sodium chloride solution, dried (MgSO4 and evaporated. The residue was purified by column chromatography using initially methylene chloride and then increasingly polar mixtures of methylene chloride and diethyl ether, up to a 1:1 v/v mixture, as eluent. There was thus obtained 1-hydroxy-2-methoxy-1-(3-methoxymethoxyphenyl)cyclopentane (3.11 g, 56%), as an oil.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - EP385663, 1995, B1

41
[ 42471-59-0 ]
[ 216443-40-2 ]

Yield	Reaction Conditions	Operation in experiment
		18.b 3-Methoxymethoxy-2'-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-[1,1';4',1"]terphenyl-4"-carboxylic Acid (b) 3-Methoxymethoxyphenylboronic Acid. In a manner similar to that of Example 1(a), starting with 125.00 g (575.8 mmol) of 3-methoxymethoxybromobenzene, 86.00 g (100%) of the expected product are obtained in the form of a yellow oil which will be used directly for the following step.
		29.b (b) (b) 3-Methoxymethoxybenzeneboronic acid: In a similar manner to that of Example 2(a), starting with 65.00 g (299.4 mmol) of 3-methoxymethoxybromobenzene obtained in Example 29(a), 30.20 g (67%) of the expected compound are obtained in the form of a beige-coloured powder with a melting point of 45° C. 1 H NMR (CDCl3) δ 3.54 (s, 3H), 5.28 (s, 2H), 7.26 to 7.54 (m, 3H), 7.86 to 7.90(m, 1H).

Reference： [1]Current Patent Assignee: Eqt Partners AB; Galderma (in: EQT Partners) - US6316009, 2001, B1
[2]Current Patent Assignee: Eqt Partners AB; Galderma (in: EQT Partners) - US6150413, 2000, A

42
BF₃ Et₂ O [ No CAS ]
spiro[oxirane-1,4'-4'H-tetrahydropyran] [ No CAS ]
[ 42471-59-0 ]
[ 144-55-8 ]
lithium anion [ No CAS ]
[ 156353-05-8 ]

Yield	Reaction Conditions	Operation in experiment
30%	With n-butyllithium In tetrahydrofuran	14.2 Preparation of 4-methoxy-4-[(3-((naphth-2-yl)methoxy)phen-1-yl)methyl]tetrahydropyran. Step 2. 4-hydroxy-4-[(3-(methyloxymethoxy)phen-1-yl)methyl]tetrahydropyran. 3-methyloxymethoxy-bromobenzene (928 mg, 4.3 mmol) was treated with n-butyllithium (2.5M solution in hexanes, 1.7 mL, 4.3 mmol) at -78° C. as described in Example 1, step 3. The -78° C. lithium anion solution was transferred to a -78° C. solution of BF3 Et2 O (0.559 mL, 4.3 mmol) in freshly dried THF (30 mL). A solution of spiro[oxirane-1,4'-4'H-tetrahydropyran] (0.5 g, 4.3 mmol), prepared as in step 1, in THF (3 mL) was added to the anion solution and the resulting solution was stirred 1.5 hours at -78° C. and then overnight at -10° C. under a nitrogen atmosphere. The reaction was quenched by the addition of excess saturated aqueous sodium bicarbonate. The volatiles were removed in vacuo and the resulting aqueous solution was extracted with ether (5*, 30 mL). The combined organic layers were washed twice with brine, dried over MgSO4, filtered, and concentrated in vacuo to provide a cloudy oil. Purification by chromatography on silica gel (35 g, 20% ethyl acetate/hexanes) provided 4-hydroxy-4-[(3-(methyloxymethoxy)phen-1-yl)methyl]tetrahydropyran (326 mg, 30%).

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - US5354865, 1994, A

43
[ 29943-42-8 ]
[ 109-87-5 ]
[ 591-20-8 ]
[ 42471-59-0 ]
[ 130722-57-5 ]
4-hydroxy-4-(3-methoxymethoxyphenyl)tetrahydropyran [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With magnesium In tetrahydrofuran	NOTES The 4-(3-hydroxyphenyl)-4-methoxytetrahydropyran used as a starting material was obtained as follows:-3-Methoxymethoxyphenyl bromide was prepared by the reaction of 3-bromophenol and dimethoxymethane using the general procedure described in Synthesis, 1976, 244. A Grignard reagent was prepared by heating a mixture of 3-methoxymethoxyphenyl bromide (6 g), magnesium (0.66 g) and tetrahydrofuran (34 ml) to 30° C. for 2 hours. The reagent was cooled to ambient temperature and a solution of tetrahydropyran-4-one (2.76 g) in tetrahydrofuran (2 ml) was added dropwise. The mixture was stirred at ambient temperature for 15 hours and evaporated. The residue was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous sodium chloride solution, dried (MgSO4) and evaporated. The residue was purified by column chromatography using a 9:1 v/v mixture of methylene chloride and diethyl ether as eluent. There was thus obtained 4-hydroxy-4-(3-methoxymethoxyphenyl)tetrahydropyran (4.5 g, 69%), as an oil.
69%	With magnesium In tetrahydrofuran	1 EXAMPLE 1 The 4-(3-hydroxyphenyl)-4-methoxytetrahydropyran used as a starting material was obtained as follows: 3-Methoxymethoxyphenyl bromide was prepared by the reaction of 3-bromophenol and dimethoxymethane using the general procedure described in Synthesis, 1976, 244. A Grignard reagent was prepared by heating a mixture of 3-methoxymethoxyphenyl bromide (6 g), magnesium (0.66 g) and tetrahydrofuran (34 ml) to 30° C. for 2 hours. The reagent was cooled to ambient temperature and a solution of tetrahydropyran-4-one (2.76 g) in tetrahydrofuran (2 ml) was added dropwise. The mixture was stirred at ambient temperature for 15 hours and evaporated. The residue was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous sodium chloride solution, dried (MgSO4) and evaporated. The residue was purified by column chromatography using a 9:1 v/v mixture of methylene chloride and diethyl ether as eluent. There was thus obtained 4-hydroxy-4-(3-methoxymethoxyphenyl)tetrahydropyran (4.5 g, 69%), as an oil.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC; AKZO NOBEL NV; WORMS LOUIS; SIEMENS AG - US5098930, 1992, A
[2]Current Patent Assignee: ASTRAZENECA PLC - US5134148, 1992, A

44
[ 123-75-1 ]
[ 53199-31-8 ]
[ 42471-59-0 ]
[ 57-09-0 ]
[ 25912-16-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In n-heptane; ethyl acetate; toluene;	B. Synthesis of 3-(1-pyrrolidinyl)phenol 7g (30 mmol) of 1-Bromo-3-methoxymethoxy-benzene from step A and 2,5 g (35 mmol) of pyrrolidine were dissolved under argon in 60 mL of toluene. Then, 0.15 g (0.3 mmol) of <strong>[53199-31-8]bis(tri-t-butylphosphine)palladium(0)</strong>, 2,5g KOH und 0,6g (0,15 mmol) cetyltrimethylammoniumbromid were added, and the reaction mixture was heated at 80 C. At the end of the reaction, the reaction mixture was poured into 200 mL of ethyl acetate, and the organic phase was extracted with 1 N sodium hydroxide solution and then dried with magnesium sulfate. The solvent was distilled off in a rotary evaporator, and the residue was purified on silica gel using heptane/ethyl acetate (8/0,8). The product thus obtained was dissolved in 15 mL of ethanol and mixed with 10 mL of a 2.9 molar solution of ethanolic hydrochloric acid.

Reference： [1]Patent: EP1752192,2007,A1

45
[ 591-20-8 ]
[ 3188-13-4 ]
[ 42471-59-0 ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile	1.A A. A. Synthesis of 1-Bromo-3-methoxymethoxy-benzene To a solution of 31.4 g (183.3 mmol) of 3-Bromo-phenol in 450 mL of dried acetonitrile a dispersion of 12 g (274.9 mmol) of sodium hydride (55% in oil) was added portionwise at 0 °C. The mixture was then allowed to agitate at 0 °C for 3 hours. A solution of 25 g (210.8 mmol) of chloromethyl ethyl ether in 30 mL of acetonitrile was added dropwise, and the mixture was allowed to agitate overnight at room temperature (20-30 °C). The reaction mixture was then filtered and the filter cake was washed with a small amount of acetone. The combined filtrates were evaporated. This gave 32.3 g of 1-Bromo-3-methoxymethoxy-benzene. The resulting crude product was used in the next step without further purification. 1H-NMR (300 MHz, DMSO): 7.26-7.16 ppm (m 3H); 7.02 ppm (dd, 1H); 5.25 ppm (s, 2H); 3.65 ppm (q, 2H); 3.5 ppm (t, 3H).

Reference： [1]Current Patent Assignee: PROCTER & GAMBLE CO - EP1752192, 2007, A1

46
[ 42471-59-0 ]
[ 1006715-24-7 ]

Yield	Reaction Conditions	Operation in experiment
71%	Stage #1: 1-bromo-3-(methoxymethoxy)benzene In tetrahydrofuran; hexane; pentane at -30℃; for 16h; Stage #2: With iodine In tetrahydrofuran; hexane; pentane at 20℃; for 1h; Further stages.;

Reference： [1]Uchiyama, Masanobu; Kobayashi, Yuri; Furuyama, Taniyuki; Nakamura, Shinji; Kajihara, Yumiko; Miyoshi, Tomoko; Sakamoto, Takao; Kondo, Yoshinori; Morokuma, Keiji [Journal of the American Chemical Society, 2008, vol. 130, # 2, p. 472 - 480]

47
[ 42471-59-0 ]
[ 60011-16-7 ]
[ 1092722-65-0 ]

Reference： [1]Tetrahedron Letters,2008,vol. 49,p. 6921 - 6923

48
[ 121-43-7 ]
[ 42471-59-0 ]
C₁₀H₁₅BO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-bromo-3-(methoxymethoxy)benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: Trimethyl borate In tetrahydrofuran; hexane at -78 - -40℃; for 1.5h;	2 [3-(methoxymethoxy)phenyl]boronic acid: Reference Example 2 [3-(methoxymethoxy)phenyl]boronic acid: A solution of the compound prepared in Reference Example 1 (32.6g) in tetrahydrofuran (600mL; THF) was cooled down to a temperature of -78°C, dropped by 1.5M n-butyllithium-hexane solution (110mL) below -60°C and then stirred by for an hour at -78°C. The mixture was dropped by trimethyl borate (50mL) below -60°C and stirred for an hour and a half with rising from -78°C to -40°C. The mixture was added by saturated ammonium chloride solution (150mL) and stirred for an hour with rising from - 10°C to 10°C. The mixture was added by water, extracted by ethyl acetate and the extract was washed with 1N hydrochloric acid, water and saturated brine successively, dried over and then concentrated. The residue was added by mixed solvent (hexane: ethyl acetate = 3: 1) to obtain crystals and the filtrate was concentrated. Solid obtained by purifying obtained residue with column and the above-mentioned obtained crystals were mixed to give the title compound (12g) having the following physical data. TLC: Rf 0.47 (hexane: ethyl acetate = 1: 1)

Reference： [1]Current Patent Assignee: ONO PHARMACEUTICAL CO LTD - EP1604971, 2005, A1 Location in patent: Page/Page column 20

49
[ 42471-59-0 ]
[ 108-24-7 ]
[ 1241953-60-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-bromo-3-(methoxymethoxy)benzene With n-butyllithium; diisopropylamine In tetrahydrofuran at -100 - 0℃; Stage #2: acetic anhydride In tetrahydrofuran at -95 - 20℃;	2 To a solution of diisopropylamine (9.85 mL, 69.1 mmol) in THF (100 mL) at -78 0C was slowly added 2.5 M «-BuLi (29.9 mL, 74.9 mmol). The solution was warmed and stirred 20 min at 0 0C, cooled to -100 °C before the slow addition of the cold THF (40 mL) solution of 1 -bromo-3 -(methoxymethoxy)benzene (12.5 g, 57.6 mmol) via a cannula. The mixture was stirred for 2 h at -100 °C, keeping the internal temperature kept between -94 0C and 101 °C. Then acetic anhydride (10.00 mL, 106 mmol) was added drop wise to the reaction mixture and internal temperature was kept below -95 °C. The final white suspension was warmed to room temperature. Then water (100 mL) was added and the volatile materials were evaporated under reduced pressure. More water was added and the aqueous media was extracted with EtOAc, and washed with brine. The aqueous phases were back extracted with EtOAc. The organic layers were combined, dried (Na2SO4), filtered and evaporated under reduced pressure. The residue was purified on chromatography column on SiO2 (120 g, gradient 0 to 15% EtOAc/hexanes) to afford the title compound as a colorless oil.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2010/94120, 2010, A1 Location in patent: Page/Page column 67-68

50
[ 42471-59-0 ]
[ 142570-56-7 ]
[ 781675-82-9 ]

Yield	Reaction Conditions	Operation in experiment
59%	Stage #1: 1-bromo-3-(methoxymethoxy)benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: [2-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester In tetrahydrofuran; hexane at -18℃; for 1h;	17.1 1-Bromo-3-(methoxymethoxy)benzene (3.938 g, 18.14 mmol) prepared from 3-bromophenol by the method described in Shin-Jikken-Kagaku-Koza (New Experiment Chemistry Lecture) Vol. 14, p.568 (Maruzen, 1978) was dissolved in tetrahydrofuran (8 mL), and to the solution was gradually added a 1.56 mol/L solution of n-butyl lithium in hexane (12.2 mL, 19.0 mmol) under cooling at -78°C. Subsequently, to the mixture was added THF (16 mL), and then the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was gradually added to tert-butyl [2-(N-methoxy-N-methylcarbamoyl)ethyl]carbamate (this compound is prepared by condensation of N-tert-butoxycarbonyl-β-alanine and N,O-dimethylhydroxylamine hydrochloride) (2.010 g, 8.653 mmol) dissolved in THF (10 mL) at -18°C. The mixture was stirred at the same temperature for 1 hour, then to the mixture was added water and saturated aqueous ammonium chloride, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1/4) to give tert-butyl {3-[3-(methoxymethoxy)phenyl]-3-oxopropyl}carbamate (1.568 g, 59%). APCI-MS m/z 310 (M+H) +.

Reference： [1]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO., LTD.; FUJIFILM HOLDINGS CORP. - EP1616866, 2006, A1 Location in patent: Page/Page column 52-53

51
[ 42471-59-0 ]
[ 1279712-55-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.25 h / -78 °C 1.2: 1.25 h / -78 °C 1.3: -78 - 20 °C 2.1: n-butyllithium / hexane; toluene / 4.25 h / -50 - 20 °C 2.2: -50 - 20 °C

Reference： [1]Neufeind, Stefan; Huelsken, Nils; Neudoerfl, Joerg-Martin; Schloerer, Nils; Schmalz, Hans-Guenther [Chemistry - A European Journal, 2011, vol. 17, # 9, p. 2633 - 2641]

52
[ 42471-59-0 ]
[ 1279712-56-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.25 h / -78 °C 1.2: 1.25 h / -78 °C 1.3: -78 - 20 °C 2.1: n-butyllithium / hexane; toluene / 4.25 h / -50 - 20 °C 2.2: -50 - 20 °C 3.1: di-isopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran / 2.5 h / 0 - 20 °C

Reference： [1]Neufeind, Stefan; Huelsken, Nils; Neudoerfl, Joerg-Martin; Schloerer, Nils; Schmalz, Hans-Guenther [Chemistry - A European Journal, 2011, vol. 17, # 9, p. 2633 - 2641]

53
[ 42471-59-0 ]
[ 245124-09-8 ]
[ 1279712-54-7 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: 1-bromo-3-(methoxymethoxy)benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #2: With cerium(III) chloride In tetrahydrofuran; hexane at -78℃; for 1.25h; Stage #3: 6-((triisopropylsilyl)oxy)hexanal In tetrahydrofuran; hexane at -78 - 20℃;

Reference： [1]Neufeind, Stefan; Huelsken, Nils; Neudoerfl, Joerg-Martin; Schloerer, Nils; Schmalz, Hans-Guenther [Chemistry - A European Journal, 2011, vol. 17, # 9, p. 2633 - 2641]

54
[ 42471-59-0 ]
C₁₂H₁₈O₃S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C / Inert atmosphere 2.1: tetrahydrofuran / 1 h / -78 - -50 °C / basic condition; Inert atmosphere 2.2: -78 - 20 °C / Inert atmosphere

Reference： [1]Liu, Jibing; Chen, Guihua; Xing, Junwei; Liao, Jian [Tetrahedron Asymmetry, 2011, vol. 22, # 5, p. 575 - 579]

55
[ 42471-59-0 ]
[ 1310329-90-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / 0.5 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C / Inert atmosphere 2.1: tetrahydrofuran / 1 h / -78 - -50 °C / basic condition; Inert atmosphere 2.2: -78 - 20 °C / Inert atmosphere 3.1: sodium hydroxide / ethanol / 0.33 h / 20 °C / Inert atmosphere 3.2: 20 °C / Inert atmosphere

Reference： [1]Liu, Jibing; Chen, Guihua; Xing, Junwei; Liao, Jian [Tetrahedron Asymmetry, 2011, vol. 22, # 5, p. 575 - 579]

56
[ 42471-59-0 ]
[ 67734-35-4 ]
[ 1310329-93-1 ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Under an argon atmosphere, to a solution of substituted bromobenzene (2.2 mmol) in THF (10 mL) was added dropwise n-BuLi (1.0 mL, 2.5 mmol) at -78 C and the mixture was stirred for 30 min. A solution of <strong>[67734-35-4](R)-tert-butyl tert-butanethiosulfinate</strong> 6 (0.39 g, 2.0 mmol) in THF (2 mL) was then added dropwise to the reaction mixture at -78 C. The temperature was allowed to slowly warm to room temperature. The reaction mixture was stirred overnight at room temperature, and then evaporated under reduced pressure. Saturated NH4Cl (10 mL) was added, and extracted with CH2Cl2 (10 mL × 3). The combined organic layers were washed with brine and dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by column chromatography with petroleum ether/EtOAc (4:1, V/V) to afford 7.13

Reference： [1]Tetrahedron Asymmetry,2011,vol. 22,p. 575 - 579

57
[ 42471-59-0 ]
(+)-aspercyclide C [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: palladium diacetate; caesium carbonate; 1,4-bis(4'-methoxyphenyl)-1,4-diazabuta-1,3-diene / 1,4-dioxane / 6 h / 120 °C 2: sodium hydride / mineral oil; tetrahydrofuran / 9 h / 40 °C 3: hydrogenchloride / methanol; tetrahydrofuran; water / 18 h / 40 °C 4: [bis(acetoxy)iodo]benzene; potassium carbonate / chlorobenzene; ethanol / 30 h / 0 - 20 °C 5: boron trichloride / dichloromethane / 0.5 h / -78 °C

Reference： [1]Yoshino, Tatsuya; Yamashita, Shuji; Sato, Itaru; Hayashi, Yujiro; Hirama, Masahiro [Chemistry Letters, 2014, vol. 43, # 3, p. 349 - 351]

58
[ 42471-59-0 ]
C₃₂H₃₈O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: palladium diacetate; caesium carbonate; 1,4-bis(4'-methoxyphenyl)-1,4-diazabuta-1,3-diene / 1,4-dioxane / 6 h / 120 °C 2: sodium hydride / mineral oil; tetrahydrofuran / 9 h / 40 °C

Reference： [1]Yoshino, Tatsuya; Yamashita, Shuji; Sato, Itaru; Hayashi, Yujiro; Hirama, Masahiro [Chemistry Letters, 2014, vol. 43, # 3, p. 349 - 351]

59
[ 42471-59-0 ]
C₃₀H₃₄O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: palladium diacetate; caesium carbonate; 1,4-bis(4'-methoxyphenyl)-1,4-diazabuta-1,3-diene / 1,4-dioxane / 6 h / 120 °C 2: sodium hydride / mineral oil; tetrahydrofuran / 9 h / 40 °C 3: hydrogenchloride / methanol; tetrahydrofuran; water / 18 h / 40 °C

Reference： [1]Yoshino, Tatsuya; Yamashita, Shuji; Sato, Itaru; Hayashi, Yujiro; Hirama, Masahiro [Chemistry Letters, 2014, vol. 43, # 3, p. 349 - 351]

60
[ 42471-59-0 ]
C₃₀H₃₂O₅ [ No CAS ]
C₃₀H₃₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: palladium diacetate; caesium carbonate; 1,4-bis(4'-methoxyphenyl)-1,4-diazabuta-1,3-diene / 1,4-dioxane / 6 h / 120 °C 2: sodium hydride / mineral oil; tetrahydrofuran / 9 h / 40 °C 3: hydrogenchloride / methanol; tetrahydrofuran; water / 18 h / 40 °C 4: [bis(acetoxy)iodo]benzene; potassium carbonate / chlorobenzene; ethanol / 30 h / 0 - 20 °C

Reference： [1]Yoshino, Tatsuya; Yamashita, Shuji; Sato, Itaru; Hayashi, Yujiro; Hirama, Masahiro [Chemistry Letters, 2014, vol. 43, # 3, p. 349 - 351]

61
[ 42471-59-0 ]
C₃₀H₃₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: palladium diacetate; caesium carbonate; 1,4-bis(4'-methoxyphenyl)-1,4-diazabuta-1,3-diene / 1,4-dioxane / 6 h / 120 °C 2: sodium hydride / mineral oil; tetrahydrofuran / 9 h / 40 °C 3: hydrogenchloride / methanol; tetrahydrofuran; water / 18 h / 40 °C 4: [bis(acetoxy)iodo]benzene; potassium carbonate / chlorobenzene; ethanol / 30 h / 0 - 20 °C

Reference： [1]Yoshino, Tatsuya; Yamashita, Shuji; Sato, Itaru; Hayashi, Yujiro; Hirama, Masahiro [Chemistry Letters, 2014, vol. 43, # 3, p. 349 - 351]

62
[ 42471-59-0 ]
[ 1393107-77-1 ]
C₂₄H₃₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With 1,4-bis(4'-methoxyphenyl)-1,4-diazabuta-1,3-diene; palladium diacetate; caesium carbonate In 1,4-dioxane at 120℃; for 6h;	Alcohol 9.² To a stirred solution of 6 (343 mg, 1.38 mmol) and 5 (200 mg, 0.921 mmol) in1,4-dioxane (18 ml) were added Pd(OAc)2 (21.0 mg, 92.1 f.Lmol), Cs2C03 (600 mg, 1.84 mmol) and N,N'-bis(4-methoxyphenyl)diazabutadiene 2 3 (49.0 mg, 0.184 mmol) at room temperature. The resulting mixture was stirred at 120 °C for 6 h, and then allowed to cool to room temperature. The reaction mixture was quenched with saturated aqueous NH4Cl, and extracted with EtO. The organic layer was washed with brine, dried over Na2S04 and concentrated. Purification of the residue by flash column chromatography (hexane/EtOAc = 20/1) gave 9 (256mg, 0.666 mmol) in 72% yield:

Reference： [1]Yoshino, Tatsuya; Yamashita, Shuji; Sato, Itaru; Hayashi, Yujiro; Hirama, Masahiro [Chemistry Letters, 2014, vol. 43, # 3, p. 349 - 351]

63
[ 42471-59-0 ]
7-ethylnaphthalene-2-carbaldehyde [ No CAS ]
2-ethylnaphthalen-7-yl[3-(methoxymethoxy)phenyl]methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: 1-bromo-3-(methoxymethoxy)benzene With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; for 0.166667h; Stage #2: 7-ethylnaphthalene-2-carbaldehyde In tetrahydrofuran; pentane at -78℃; for 1h;	11 4.1.11 2-Ethylnaphthalen-7-yl[3-(methoxymethoxy)phenyl]methanol (27) A solution of 26 15 (533 mg, 2.46 mmol) in THF (16.0 mL) was treated with t-BuLi (1.59 M sol. in pentane, 3.09 mL, 4.91 mmol) at -78 °C. After stirring for 10 min at -78 °C, 25 (302 mg, 1.63 mmol) in THF (8.6 mL) was added. After stirring for 1 h at -78 °C, the reaction mixture was quenched with satd NH4Cl aq The aqueous layer was extracted with EtOAc. The organic layers were combined, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash silica gel column chromatography (10:1 hexanes/EtOAc) to afford 27 (523 mg, 99%) as a white solid. IR (KBr) 3448, 2964, 2347, 1633, 1605, 1511, 1486, 1451, 1403, 1314, 1246, 1207, 1150 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.86 (s, 1H), 7.79 (d, J = 8.6 Hz, 1H), 7.77 (d, J = 8.6 Hz, 1H), 7.66 (s, 1H), 7.42 (dd, J = 6.6 Hz, 1H), 7.37 (dd, J = 6.6 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.17 (s, 1H), 7.08 (d, J = 7.6 Hz, 1H), 7.01-6.97 (m, 1H), 6.00 (d, J = 3.3 Hz, 1H), 5.20 (s, 2H), 3.50 (s, 3H), 2.86 (q, J = 7.6 Hz, 2H), 1.36 (t, J = 7.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 157.4, 145.4, 142.1, 141.0, 133.5, 131.3, 129.5, 128.0, 127.5, 127.2, 125.7, 124.7, 123.9, 120.2, 115.1, 114.7, 94.4, 76.2, 56.0, 29.0, 15.5 ; HRMS (ESI) [M+Na]+ calcd for C21H22O3Na 345.1467, found 345.1464.

Reference： [1]Ohtawa, Masaki; Matsunaga, Mari; Fukunaga, Keiko; Shimizu, Risa; Shimizu, Eri; Arima, Shiho; Ohmori, Junko; Kita, Kiyoshi; Shiomi, Kazuro; Omura, Satoshi; Nagamitsu, Tohru [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 5, p. 932 - 943]

64
[ 42471-59-0 ]
tert-butyl 4-(2-(2-chloro-5-(methoxymethoxy)phenyl)-6-(3,5-dimethylisoxazol-4-yl)-5-methylpyrimidin-4-ylamino)-3,3-difluoropiperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.33 h / -78 °C / Inert atmosphere 1.2: 0.67 h / -78 °C / Inert atmosphere 1.3: 0.5 h / Inert atmosphere 2.1: sodium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / 1,4-dioxane; water / 2 h / 80 °C / Inert atmosphere 3.1: N-chloro-succinimide / N,N-dimethyl-formamide / 2 h / 45 °C 4.1: potassium fluoride / dimethyl sulfoxide / 6 h / 120 °C / Sealed tube; Microwave irradiation