Name: 123387-50-8|tert-Butyl 4-methylpiperidine-1-carboxylate|97%
Brand: Ambeed
SKU: A300732
Rating: 90 (29 reviews)

1
[ 124-38-9 ]
[ 123387-50-8 ]
[ 123811-83-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: 4-methylpiperidine-1-carboxylic acid tert-butyl ester With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether; cyclohexane at -78 - 20℃; for 1h; Stage #2: carbon dioxide In diethyl ether; cyclohexane at -78℃; for 0.25h;	6 Preparation of compound 55 A solution of compound 54 (926.5 mg, 5.0 mmol) in Et2O (10.5 mL) was cooled to -78°C and treated with TMEDA (755 µL, 5.0 mmol) followed by slow addition of a 1.3 M cyclohexane solution of sec-butyllithium (4.6 mL, 6.0 mmol) over a 30 minute period. The reaction solution was then warmed to -20°C and maintained at that temperature for 30 minutes, after which the solution was re-cooled to -78°C and purged with gaseous carbon dioxide for 15 minutes. The reaction solution was then slowly warmed to 0°C and poured into a biphasic mixture of 1 N HCl (100 mL) and EtOAc (50 mL). The reaction solution was then extracted several times with EtOAc. The EtOAc extracts were combined, dried over Mg2SO4, filtered, and concentrated to provide compound 55 (1.07 g) in 89% yield as a colorless oil (a mixture of two cis enantiomers).
60 % Turnov.	With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether at -90 - 20℃; for 5h;

Reference： [1]Current Patent Assignee: EISAI CO LTD - EP2374454, 2016, B1 Location in patent: Paragraph 0133; 0134
[2]Cossy, Janine; Belotti, Damien [Tetrahedron Letters, 2001, vol. 42, # 11, p. 2119 - 2120]

2
[ 541-41-3 ]
[ 123387-50-8 ]
4-methyl-piperidine-1,2-dicarboxylic acid 1-<i>tert</i>-butyl ester 2-ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60 % Turnov.	With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether at -90 - 20℃; for 5h;

Reference： [1]Cossy, Janine; Belotti, Damien [Tetrahedron Letters, 2001, vol. 42, # 11, p. 2119 - 2120]

3
[ 123387-50-8 ]
[ 501-53-1 ]
benzyl trans-N-Boc-4-methylpipecolic acid ester [ No CAS ]
(2R,4S)-4-Methyl-piperidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether at -90 - 20℃; for 5h;

Reference： [1]Cossy, Janine; Belotti, Damien [Tetrahedron Letters, 2001, vol. 42, # 11, p. 2119 - 2120]

4
[ 123387-50-8 ]
[ 79-22-1 ]
4-methyl-piperidine-1,2-dicarboxylic acid 1-<i>tert</i>-butyl ester 2-methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58 % Turnov.	With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether at -90 - 20℃; for 5h;

Reference： [1]Cossy, Janine; Belotti, Damien [Tetrahedron Letters, 2001, vol. 42, # 11, p. 2119 - 2120]

5
[ 626-58-4 ]
[ 24424-99-5 ]
[ 123387-50-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine In dichloromethane at 0 - 20℃;
97%	With iron(III) trifluoromethanesulfonate In neat (no solvent) at 20℃; for 0.0833333h; Green chemistry;	N-Boc protection of amines General procedure: Fe(OTf)3 (1 mol%) was added to a magnetically stirred mixture of anamine (1 mmol) and Boc2O (1 mmol) at room temperature. The mixturewas stirred until completion of the reaction (TLC), then diluted withEtOAc and washed with water. The organic layer was dried overanhydrous MgSO4, then the solvent was distillated off under vacuum toyield the highly pure N-Boc derivatives
81%	With dimethylbromosulphonium bromide at 20℃; for 0.0833333h; neat (no solvent);

78%	With iodine at 20℃; for 2.33333h;
73%	With triethylamine In dichloromethane at 35℃; for 3h;	1.a Preparation 1; (4-Methyl-1-nitroso-2-oxo-1,2,5,6-tetrahydropyridin-3-yl)acetic acid ethyl ester; (a) 4-Methvlpiperidine-l-carboxylic acid tert-butyl ester; 4-Methylpiperidine (5.0 g, 50 mmol) and di-tert-butyl dicarbonate (13 g, 60 mmol) were dissolved in DCM (50 mL). TEA (7.65 mL, 1. 1 mol equiv.) was added and the reaction mixture was stirred at 35°C for 3 hours. The solvent was removed in vacuo and the residue was purified by flash chromatography (Si02, hexane) to give the sub-title compound (7.29 g, 73%). 1H NMR (400 MHz, CDC13) 6 0. 81 (d, 3H), 0.86-1. 00 (m, 2H), 1.33 (s, 9H), 1.13-1. 49 (m, 3H), 2.55 (m, 2H), 3.93 (m, 2H)
73%	With triethylamine In dichloromethane at 35℃;
73%	With triethylamine In dichloromethane at 35℃; for 3h;	1.a Preparation 1 (1-Amino-4-methyl-2-oxo-l,2,5,6-tetrahvdropyridin-3-yl)acetic acid ethyl ester (a) 4-Methyrpiperidine-l-carboxylic acid fert-butyl ester 4-Methylpiperidine (5.0 g, 50 mmol) and dhtert -butyl dicarbonate (13 g, 60 mmol) were dissolved in DCM (50 mL). TEA (7.65 mL, 1.1 mol equiv.) was EPO added and the reaction mixture was stirred at 35°C for 3 hours. The solvent was removed in vacuo and the residue was purified by flash chromatography (SiO2, hexane) to give the sub-title compound (7.29 g, 73%).1H NMR (400 MHz5 CDQ) δ 0.81 (d, 3H), 0.86 - 1.00 (m, 2H), 1.33 (s, 9H), 1.13 - 1.49 (m, 3H), 2.55 (m, 2H), 3.93 (m, 2H)
	With sodium hydroxide In tetrahydrofuran; water at 20℃; Cooling with ice;
926.5 mg	With triethylamine at 0 - 20℃;	6 Preparation of compound 54 To a solution of 4-methylpiperidine (53) (600 µL, 5.0 mmol) in MeOH (20 mL) was added Et3N (770 µL, 5.5 mmol) followed by Boc2O (1.2 g, 5.5 mmol) at 0°C. After 15 minutes, the reaction mixture was warmed to room temperature and allowed to stir overnight. The reaction solution was then diluted with H2O and extracted several times with ether. The ether extracts were combined, dried over Mg2SO4, filtered, and concentrated to provide compound 54 (926.5 mg) quantitatively as a colorless oil.
	With dmap In toluene at 0 - 20℃; for 0.5h; Inert atmosphere;	N-Boc-trans-4-methyl-2-phenylthiopiperidine (1b). To a solution of 4-methylpiperidine (1.98 g, 20.0mmol) and DMAP (0.0999 g, 0.818 mmol) in toluene (30 mL) was added slowly (Boc)2O (4.59 mL, 4.80 g,22.0 mmol) at 0 °C. After being stirred at room temperature for 30 min, the reaction was quenched withwater. The solvent was removed under reduced pressure. The residue was quickly filtered through a shortcolumn of alumina. The combined solution was concentrated to give crude tert-butyl4-methylpiperidinecarboxylate (3.35 g, 12.9 mmol, 65%) which was used directly for the next step. To asolution of tert-butyl 4-methylpiperidinecarboxylate (3.35 g, 12.9 mmol) in dry Et2O (17 mL) was slowlyadded TMEDA (2.51 mL, 1.95 g, 16.8 mmol) at -78 °C, followed by dropwise addition of sec-BuLi (1.02 Min hexane, 16.5 mL, 16.8 mmol) at the same temperature. Then the mixture was slowly warmed to -40 °C,stirred for 30 min, and then cooled again to -78 °C. To this mixture was added dropwise diphenyl disulfide(PhSSPh, 11.3 g, 51.6 mmol) in Et2O (22 mL). Then the mixture was slowly allowed to warm to roomtemperature and stirred for 24 h. The reaction mixture was quenched with water (30 mL), extracted withEt2O (3×30 mL). The combined organic phase was washed with saturated aqueous NaHCO3 (30 mL), driedover MgSO4, and concentrated under reduced pressure. The residue was purified by flash chromatography(hexane/EtOAc 30:1 to 10:1) to obtain the title compound (9.90 g, 3.22 mmol, 25%)

Reference： [1]Cossy, Janine; Belotti, Damien [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 15, p. 1989 - 1992]
[2]Feng, Chengliang; Chu, Ningning; Zhang, Shuguang; Cai, Jin; Chen, Junqing; Hu, Huayou; Ji, Min [Journal of Chemical Research, 2013, vol. 37, # 12, p. 757 - 760]
[3]Location in patent: experimental part Shailaja; Manjula; Vittal Rao [Synthetic Communications, 2011, vol. 41, # 14, p. 2073 - 2080]
[4]Varala, Ravi; Nuvula, Sreelatha; Adapa, Srinivas R. [Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 8283 - 8286]
[5]Current Patent Assignee: ASTRAZENECA PLC - WO2005/58826, 2005, A1 Location in patent: Page/Page column 88
[6]Location in patent: scheme or table Hanessian, Stephen; Therrien, Eric; Zhang, Jianbin; Otterlo, Willem van; Xue, Yafeng; Gustafsson, David; Nilsson, Ingemar; Fjellstroem, Ola [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 18, p. 5429 - 5432]
[7]Current Patent Assignee: ASTRAZENECA PLC - WO2006/135323, 2006, A1 Location in patent: Page/Page column 52-53
[8]Cui, Li; Peng, Yu; Zhang, Liming [Journal of the American Chemical Society, 2009, vol. 131, p. 8394 - 8395]
[9]Current Patent Assignee: EISAI CO LTD - EP2374454, 2016, B1 Location in patent: Paragraph 0131; 0132
[10]Mitsudo, Koichi; Yamamoto, Junya; Akagi, Tomoya; Yamashita, Atsuhiro; Haisa, Masahiro; Yoshioka, Kazuki; Mandai, Hiroki; Ueoka, Koji; Hempel, Christian; Yoshida, Jun-ichi; Suga, Seiji [Beilstein Journal of Organic Chemistry, 2018, vol. 14, p. 1192 - 1202]

6
[ 123387-50-8 ]
[ 501-53-1 ]
benzyl trans-N-Boc-4-methylpipecolic acid ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	Stage #1: 4-methylpiperidine-1-carboxylic acid tert-butyl ester With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether at -90℃; Stage #2: benzyl chloroformate In diethyl ether at -90 - 20℃;

Reference： [1]Cossy, Janine; Belotti, Damien [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 15, p. 1989 - 1992]

7
[ 24424-99-5 ]
[ 544478-11-7 ]
[ 123387-50-8 ]

Yield	Reaction Conditions	Operation in experiment
89%	With PMHS In ethanol at 20℃; for 5h;

Reference： [1]Chandrasekhar; Babu, B. Nagendra; Reddy, Ch. Raji [Tetrahedron Letters, 2003, vol. 44, # 10, p. 2057 - 2059]

8
[ 123387-50-8 ]
[ 74863-84-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: s-BuLi; TMEDA / diethyl ether / -90 °C 1.2: 35 percent / diethyl ether / -90 - 20 °C 2.1: 99 percent / HCl / ethyl acetate / 0 - 20 °C 3.1: 100 percent / HCl / ethyl acetate / 20 °C 4.1: 86 percent / Et₃N / CH₂Cl₂ / 0 °C 5.1: 90 percent / H₂ / 10 percent Pd/C / ethanol; acetic acid / 20 h / 20 °C / 760 Torr

Reference： [1]Cossy, Janine; Belotti, Damien [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 15, p. 1989 - 1992]

9
[ 123387-50-8 ]
trans-benzyl 4-methylpipecolic acid ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: s-BuLi; TMEDA / diethyl ether / -90 °C 1.2: 35 percent / diethyl ether / -90 - 20 °C 2.1: 99 percent / HCl / ethyl acetate / 0 - 20 °C
	Multi-step reaction with 2 steps 1: sec-BuLi; TMEDA / diethyl ether / 5 h / -90 - 20 °C 2: 100 percent / HCl / ethyl acetate

Reference： [1]Cossy, Janine; Belotti, Damien [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 15, p. 1989 - 1992]
[2]Cossy, Janine; Belotti, Damien [Tetrahedron Letters, 2001, vol. 42, # 11, p. 2119 - 2120]

10
[ 123387-50-8 ]
[ 367952-82-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: s-BuLi; TMEDA / diethyl ether / -90 °C 1.2: 35 percent / diethyl ether / -90 - 20 °C 2.1: 99 percent / HCl / ethyl acetate / 0 - 20 °C

Reference： [1]Cossy, Janine; Belotti, Damien [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 15, p. 1989 - 1992]

11
[ 123387-50-8 ]
C₂₅H₃₈N₆O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: s-BuLi; TMEDA / diethyl ether / -90 °C 1.2: 35 percent / diethyl ether / -90 - 20 °C 2.1: 99 percent / HCl / ethyl acetate / 0 - 20 °C

Reference： [1]Cossy, Janine; Belotti, Damien [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 15, p. 1989 - 1992]

12
[ 123387-50-8 ]
[ 367952-84-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: s-BuLi; TMEDA / diethyl ether / -90 °C 1.2: 35 percent / diethyl ether / -90 - 20 °C 2.1: 99 percent / HCl / ethyl acetate / 0 - 20 °C 3.1: 100 percent / HCl / ethyl acetate / 20 °C 4.1: 86 percent / Et₃N / CH₂Cl₂ / 0 °C

Reference： [1]Cossy, Janine; Belotti, Damien [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 15, p. 1989 - 1992]

13
[ 123387-50-8 ]
C₂₀H₃₀N₆O₅*ClH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: s-BuLi; TMEDA / diethyl ether / -90 °C 1.2: 35 percent / diethyl ether / -90 - 20 °C 2.1: 99 percent / HCl / ethyl acetate / 0 - 20 °C 3.1: 100 percent / HCl / ethyl acetate / 20 °C

Reference： [1]Cossy, Janine; Belotti, Damien [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 15, p. 1989 - 1992]

14
[ 123387-50-8 ]
[ 66937-93-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 60 percent Turnov_. / sec-BuLi; TMEDA / diethyl ether / 5 h / -90 - 20 °C 2: 100 percent / HCl / ethyl acetate

Reference： [1]Cossy, Janine; Belotti, Damien [Tetrahedron Letters, 2001, vol. 42, # 11, p. 2119 - 2120]

15
[ 123387-50-8 ]
methyl pipecolinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 58 percent Turnov_. / sec-BuLi; TMEDA / diethyl ether / 5 h / -90 - 20 °C 2: 100 percent / HCl / ethyl acetate

Reference： [1]Cossy, Janine; Belotti, Damien [Tetrahedron Letters, 2001, vol. 42, # 11, p. 2119 - 2120]

16
[ 123387-50-8 ]
[ 1421636-12-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	With ruthenium(IV) oxide; sodium periodate In water; ethyl acetate	1.b (b) 4-Methvl-2-oxopiperidine-1-carboxylic acid test-butyl ester; 4-Methyl-piperidine-l-carboxylic acid tert-butyl ester (1. 1 g, 5.5 mmol ; see step (a) above) was dissolved in ethyl acetate (70 mL) and was added to a solution of ruthenium oxide (0.020 g, 0.15 mmol) and sodium periodate (4.5 g, 21 mmol) dissolved in water (215 mL). The reaction was stirred vigorously under air for 18 hours. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic extracts were dried and filtered through Celiteg. The solvent was removed in vacuo and the residue (the sub-title compound-0.98 g, 83%) was used without further purification. 1H NMR (400 MHz, CDC13) 8 1. 02 (d, 3H), 1.43-1. 57 (m, 1H), 1.53 (s, 9H), 1.90-2. 03 (m, 2H), 2.04-2. 30 (m, 1H), 2.56-2. 62 (m, 1H), 3.46- 3.53 (m, 1H), 3.78-3. 82 (m, 1H)
83%	With sodium periodate; ruthenium(IV) oxide hydrate In water; ethyl acetate
83%	With ruthenium(IV) oxide; sodium periodate In water; ethyl acetate for 18h;	1.b (b) 4-Methyl-2-oxopiperidine-l-carboxylic acid tert-bτtiyl ester 4-Methyl-piperidine-l-carboxylic acid tert-buty ester (1.1 g, 5.5 mmol; see step (a) above) was dissolved in ethyl acetate (70 mL) and was added to a solution of ruthenium oxide (0.020 g, 0.15 mmol) and sodium periodate (4.5 g, 21 mmol) dissolved in water (215 mL). The reaction was stirred vigorously under air for 18 hours. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic extracts were dried and filtered through Celite. The solvent was removed in vacuo and the residue (the sub -title compound - 0.98 g, 83%) was used without further purification.1H NMR (400 MHz, CDClj) δ 1.02 (d, 3H), 1.43 - 1.57 (m, IH), 1.53 (s, 9H), 1.90 - 2.03 (m, 2H), 2.04 - 2.30 (m, IH), 2.56 - 2.62 (m, IH), 3.46 - 3.53 (m, IH), 3.78 - 3.82 (m, IH)

70%	With ruthenium(IV) oxide; sodium periodate In water; ethyl acetate for 3h;	8.2 1 g (5.02 mmol) of 4-methyl-piperidin-l-carboxylic acid t-butylester obtained in the above step (1) was dissolved in 70 mL of ethylacetate. To the resulting solution, was dropwise added a solution in which 5.4 g (25.2 mmol) of sodium periodateand and 247 mg (1.85 mmol) of ruthenium dioxide were dissolved in 40 mL of water. After 3 hours, 5% sodium thiosulfate was added thereto, and the resulting solution was extracted with ethylacetate, then an organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, then the residue was purified by column chromatography to give 750 mg (3.52 mmol) of the title compound in a yield of 70%.[435] NMR: 1H-NMR(CDCl ) δ 4.11~3.77(1H, m), 3.53~3.49(1H, m), 2.62~2.56(1H, m),2.15~1.90(3H, m), 1.49(9H, s), 1.48~1.26(1H, m), 1.02(3H, d J=4Hz)[436] Mass(EI) 214(M++.)
	With sodium periodate; ruthenium (IV) oxide monohydrate In water; ethyl acetate at 20℃; for 2h;

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2005/58826, 2005, A1 Location in patent: Page/Page column 88-89
[2]Location in patent: scheme or table Hanessian, Stephen; Therrien, Eric; Zhang, Jianbin; Otterlo, Willem van; Xue, Yafeng; Gustafsson, David; Nilsson, Ingemar; Fjellstroem, Ola [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 18, p. 5429 - 5432]
[3]Current Patent Assignee: ASTRAZENECA PLC - WO2006/135323, 2006, A1 Location in patent: Page/Page column 53
[4]Current Patent Assignee: LG CHEM CO.,LTD. - WO2006/104356, 2006, A1 Location in patent: Page/Page column 31
[5]Cui, Li; Peng, Yu; Zhang, Liming [Journal of the American Chemical Society, 2009, vol. 131, p. 8394 - 8395]

17
[ 123387-50-8 ]
[ 100-52-7 ]
cis-erythro-7-methyl-1-phenylhexahydro[1,3]oxazolo[3,4-a]pyridin-3-one [ No CAS ]
cis-threo-7-methyl-1-phenylhexahydro[1,3]oxazolo[3,4-a]pyridin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-methylpiperidine-1-carboxylic acid tert-butyl ester With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether; cyclohexane at -70 - -30℃; for 0.5h; Stage #2: benzaldehyde In diethyl ether; cyclohexane at -30 - 20℃; for 12h; Stage #3: With water In diethyl ether; cyclohexane	2.1 2.1. 2.1. Cis-7-methyl-1-phenylhexahydro[1,3]oxazolo[3,4-a]pyridin-3-one 14.2 g (71.2 mmol) of 1,1-dimethylethyl 4-methylpiperidine-1-carboxylate dissolved in 130 ml of anhydrous diethyl ether are introduced into a 1 l round-bottomed flask, under an argon atmosphere, and the medium is cooled to -70° C. 14 ml (92.5 mmol) of TMEDA (N,N,N',N'-tetramethylethylenediamine) are added, followed by addition of 70 ml (92.5 mmol) of a 1.3M solution of sec-butyllithium in cyclohexane, and the mixture is allowed to return to -30° C. with stirring over 0.5 hour. A solution of 11.33 ml (106.8 mmol) of benzaldehyde (distilled beforehand) in 40 ml of anhydrous diethyl ether is then added and the mixture is allowed to return to room temperature with stirring over 12 hours. After hydrolysis with water, the aqueous phase is separated out and extracted with ethyl acetate. The combined organic phases are dried over sodium sulfate, filtered and concentrated under reduced pressure, and the residue is purified by column chromatography on silica gel, eluding with a mixture of dichloromethane and methanol. 3.3 g of a colorless oil of a mixture of cis threo/erythro isomers are obtained.

Reference： [1]Current Patent Assignee: SANOFI - US2006/223861, 2006, A1 Location in patent: Page/Page column 5

18
[ 15854-87-2 ]
[ 123387-50-8 ]
cis-t-butyl 4-methyl-2-(pyridin-4-yl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: 4-methylpiperidine-1-carboxylic acid tert-butyl ester With sec.-butyllithium; Trimethylenediamine In diethyl ether; hexane at -78℃; for 4h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; diethyl ether; hexane at -78 - 20℃; for 0.25h; Inert atmosphere; Stage #3: 4-iodopyridine With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In tetrahydrofuran at 55℃; Inert atmosphere; optical yield given as %de; diastereoselective reaction;

Reference： [1]Seel, Stephanie; Thaler, Tobias; Takatsu, Keishi; Zhang, Cong; Zipse, Hendrik; Straub, Bernd F.; Mayer, Peter; Knochel, Paul [Journal of the American Chemical Society, 2011, vol. 133, # 13, p. 4774 - 4777]

19
[ 625-99-0 ]
[ 123387-50-8 ]
cis-t-butyl 2-(3-chlorophenyl)-4-methylpiperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: 4-methylpiperidine-1-carboxylic acid tert-butyl ester With sec.-butyllithium; Trimethylenediamine In diethyl ether; hexane at -78℃; for 4h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; diethyl ether; hexane at -78 - 20℃; for 0.25h; Inert atmosphere; Stage #3: 3-iodochlorobenzene With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In tetrahydrofuran at 55℃; Inert atmosphere; optical yield given as %de; diastereoselective reaction;

Reference： [1]Seel, Stephanie; Thaler, Tobias; Takatsu, Keishi; Zhang, Cong; Zipse, Hendrik; Straub, Bernd F.; Mayer, Peter; Knochel, Paul [Journal of the American Chemical Society, 2011, vol. 133, # 13, p. 4774 - 4777]

20
[ 696-62-8 ]
[ 123387-50-8 ]
cis-t-butyl 2-(4-methoxyphenyl)-4-methylpiperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: 4-methylpiperidine-1-carboxylic acid tert-butyl ester With sec.-butyllithium; Trimethylenediamine In diethyl ether; hexane at -78℃; for 4h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; diethyl ether; hexane at -78 - 20℃; for 0.25h; Inert atmosphere; Stage #3: para-iodoanisole With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In tetrahydrofuran at 55℃; Inert atmosphere; optical yield given as %de; diastereoselective reaction;

Reference： [1]Seel, Stephanie; Thaler, Tobias; Takatsu, Keishi; Zhang, Cong; Zipse, Hendrik; Straub, Bernd F.; Mayer, Peter; Knochel, Paul [Journal of the American Chemical Society, 2011, vol. 133, # 13, p. 4774 - 4777]

21
[ 69113-59-3 ]
[ 123387-50-8 ]
cis-t-butyl 2-(3-cyanophenyl)-4-methylpiperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: 4-methylpiperidine-1-carboxylic acid tert-butyl ester With sec.-butyllithium; Trimethylenediamine In diethyl ether; hexane at -78℃; for 4h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; diethyl ether; hexane at -78 - 20℃; for 0.25h; Inert atmosphere; Stage #3: 3-iodobenzonitrile With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In tetrahydrofuran at 55℃; Inert atmosphere; optical yield given as %de; diastereoselective reaction;

Reference： [1]Seel, Stephanie; Thaler, Tobias; Takatsu, Keishi; Zhang, Cong; Zipse, Hendrik; Straub, Bernd F.; Mayer, Peter; Knochel, Paul [Journal of the American Chemical Society, 2011, vol. 133, # 13, p. 4774 - 4777]

22
[ 455-13-0 ]
[ 123387-50-8 ]
cis-t-butyl 4-methyl-2-(4-(trifluoromethyl)phenyl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: 4-methylpiperidine-1-carboxylic acid tert-butyl ester With sec.-butyllithium; Trimethylenediamine In diethyl ether; hexane at -78℃; for 4h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; diethyl ether; hexane at -78 - 20℃; for 0.25h; Inert atmosphere; Stage #3: 4-Iodobenzotrifluoride With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In tetrahydrofuran at 55℃; Inert atmosphere; optical yield given as %de; diastereoselective reaction;

Reference： [1]Seel, Stephanie; Thaler, Tobias; Takatsu, Keishi; Zhang, Cong; Zipse, Hendrik; Straub, Bernd F.; Mayer, Peter; Knochel, Paul [Journal of the American Chemical Society, 2011, vol. 133, # 13, p. 4774 - 4777]

23
[ 51934-41-9 ]
[ 123387-50-8 ]
cis-t-butyl 2-(4-(ethoxycarbonyl)phenyl)-4-methylpiperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: 4-methylpiperidine-1-carboxylic acid tert-butyl ester With sec.-butyllithium; Trimethylenediamine In diethyl ether; hexane at -78℃; for 4h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; diethyl ether; hexane at -78 - 20℃; for 0.25h; Inert atmosphere; Stage #3: 4-iodobenzoic acid ethyl ester With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In tetrahydrofuran at 55℃; Inert atmosphere; optical yield given as %de; diastereoselective reaction;

Reference： [1]Seel, Stephanie; Thaler, Tobias; Takatsu, Keishi; Zhang, Cong; Zipse, Hendrik; Straub, Bernd F.; Mayer, Peter; Knochel, Paul [Journal of the American Chemical Society, 2011, vol. 133, # 13, p. 4774 - 4777]

24
[ 123387-50-8 ]
[ 1346152-93-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / water; tetrahydrofuran; N,N-dimethyl-formamide / 4 h / 20 - 60 °C 2: piperidine / methanol / 2 h / 60 °C

Reference： [1]Current Patent Assignee: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN); THE UNIVERSITY OF TOKYO - EP2565192, 2013, A1

25
[ 123387-50-8 ]
[ 1346150-72-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium carbonate; bis-triphenylphosphine-palladium(II) chloride / water; tetrahydrofuran; N,N-dimethyl-formamide / 4 h / 20 - 60 °C 2: piperidine / methanol / 2 h / 60 °C 3: hydrogenchloride / dichloromethane; 1,4-dioxane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN); THE UNIVERSITY OF TOKYO - EP2565192, 2013, A1

26
[ 1344715-22-5 ]
[ 123387-50-8 ]
[ 1346152-92-8 ]

Yield	Reaction Conditions	Operation in experiment
7%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In tetrahydrofuran; water; N,N-dimethyl-formamide at 20 - 60℃; for 4h;	B54.3 (c) Step 3 A solution of 7-iodo-6-methoxybenzofuran-3(2H)-one (0.290 g, 1.00 mmol) synthesized in Example B46, Step 2 in DMF (6 mL) was added with water (0.6 mL) and potassium carbonate (0.276 g, 2.00 mmol), and the mixture was stirred at room temperature, and added dropwise with the THF solution prepared in Step 2. The reaction mixture was added with [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.0732 g, 0.100 mmol), and the mixture was stirred at 60°C for 4 hours. The reaction mixture was filtered through Celite, the filtrate was added with water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain tert-butyl 4-[(6-methoxy-3-oxo-2,3-dihydrobenzofuran-7-yl)methyl]piperidine-1-carboxylate (0.0263 g, 7%). 1H NMR (300 MHz, CDCl3) δ 1.15-1.29 (m, 2H), 1.45 (s, 9H), 1.56-1.59 (m, 2H), 1.75 (m, 1H), 2.60 (d, J = 7.3 Hz, 2H), 2.65-2.69 (m, 2H), 3.91 (s, 3H), 4.03-4.07 (m, 2H), 4.61 (s, 2H), 6.68 (d, J = 8.8 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H).

Reference： [1]Current Patent Assignee: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN); THE UNIVERSITY OF TOKYO - EP2565192, 2013, A1 Location in patent: Paragraph 0534

27
[ 159635-49-1 ]
[ 123387-50-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	With palladium on activated charcoal; hydrogen In methanol for 24h; Inert atmosphere;
	With 9-bora-bicyclo[3.3.1]nonane In tetrahydrofuran for 1h; Reflux;	B54.2 (b) Step 2 [0533] A solution of tert-butyl 4-methylenepiperidine-1-carboxylate (0.256 g, 1.30 mmol) in THF (2 mL) was added dropwise with a 0.5 M solution of 9-BBN in THF (2.60 mL, 1.30 mmol). The reaction mixture was refluxed for 1 hour by heating, and then cooled to room temperature.

Reference： [1]McManus, Joshua B.; Onuska, Nicholas P. R.; Nicewicz, David A. [Journal of the American Chemical Society, 2018, vol. 140, # 29, p. 9056 - 9060]
[2]Current Patent Assignee: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN); THE UNIVERSITY OF TOKYO - EP2565192, 2013, A1 Location in patent: Paragraph 0533

28
[ 108-86-1 ]
[ 123387-50-8 ]
tert-butyl (4R)-4-methyl-2-phenylpiperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	Stage #1: 4-methylpiperidine-1-carboxylic acid tert-butyl ester With N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium In diethyl ether; cyclohexane at -78℃; for 3h; Inert atmosphere; Stage #2: With zinc(II) chloride In tetrahydrofuran; diethyl ether; cyclohexane at -78 - 20℃; for 1.75h; Inert atmosphere; Stage #3: bromobenzene With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 2-(diisopropylphosphino)-1-phenyl-1H-pyrrole In toluene at 80℃; for 17h; Inert atmosphere; diastereoselective reaction;

Reference： [1]Millet, Anthony; Baudoin, Olivier [Organic Syntheses, 2016, vol. 92, p. 76 - 90]

29
[ 123387-50-8 ]
C₂₅H₄₅N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: N,N,N,N,-tetramethylethylenediamine; sec.-butyllithium / diethyl ether; cyclohexane / 1 h / -78 - 20 °C 1.2: 0.25 h / -78 °C 2.1: 3.25 h / 0 - 20 °C 3.1: palladium(II) hydroxide; hydrogen / water; methanol 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / dichloromethane / 0.08 h 4.2: 0.5 h