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Chemical Structure| 118811-07-7
Chemical Structure| 118811-07-7
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Product Details of [ 118811-07-7 ]

CAS No. :118811-07-7 MDL No. :MFCD06796535
Formula : C17H25NO5S Boiling Point : -
Linear Structure Formula :- InChI Key :IKOMRHLHPZAEMV-UHFFFAOYSA-N
M.W : 355.45 Pubchem ID :15734713
Synonyms :

Calculated chemistry of [ 118811-07-7 ]

Physicochemical Properties

Num. heavy atoms : 24
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.59
Num. rotatable bonds : 6
Num. H-bond acceptors : 5.0
Num. H-bond donors : 0.0
Molar Refractivity : 95.26
TPSA : 81.29 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.33 cm/s

Lipophilicity

Log Po/w (iLOGP) : 3.56
Log Po/w (XLOGP3) : 3.01
Log Po/w (WLOGP) : 3.8
Log Po/w (MLOGP) : 2.51
Log Po/w (SILICOS-IT) : 1.69
Consensus Log Po/w : 2.91

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.73
Solubility : 0.0663 mg/ml ; 0.000187 mol/l
Class : Soluble
Log S (Ali) : -4.38
Solubility : 0.0148 mg/ml ; 0.0000415 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -3.8
Solubility : 0.0563 mg/ml ; 0.000158 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.15

Safety of [ 118811-07-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 118811-07-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 118811-07-7 ]
  • Downstream synthetic route of [ 118811-07-7 ]

[ 118811-07-7 ] Synthesis Path-Upstream   1~9

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  • [ 109384-19-2 ]
  • [ 118811-07-7 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine In dichloromethane at 20℃; for 20 h; To a solution of compound (33) (5 g, 1 eq., 24.8 mmol) in dichloromethane (50 mL) wasadded triethylamine (13.9 mL, 4 eq., 99.4 mmol) and p-toluenesulfonyl chloride (9.47 g, 2eq., 49.7 mmol). The solution was stirred for 20h at room temperature followed by the concentration of this solution in vacuo. The residue was then dissolved in dichloromethane (20 mL) and water (20 mL), extracted with DCM (20 mL), washed with 1 N HCl (40 mL), extracted twice with DCM (2 x 40 mL), dried over Mg504 andevaporated. The resulting mixture was then purified by silica gel column chromatography (Petroleum ether/EtOAc 8:2) and compound (34) was obtained as a white crystalline solid (8.7g, quantitative yield)
89% With triethylamine In dichloromethane at 20℃; To a solution of 1 ,1 -dimethylethyl 4-hydroxy-1 -piperidinecarboxylate (5 g, 24.8 mmol) in dichloromethane (80 ml.) was added p-toluenesulphonyl chloride (5.67 g, 190.65 mmol) and triethyl amine (5.15 ml_, 37.2 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with water (50 ml.) and dichloromethane (80 ml_). The aqueous phase was separated and extracted with dichloromethane (2x80 ml_). Pyridine was added to the combined organic phases and stood overnight. The solution was washed withi N HCI (100 ml_), separated, dried over MgSψ4 filtered and concentrated to give 1 ,1 -dimethylethyl 4-[(4-methylphenyl)sulfonyl] oxy}-1 -piperidinecarboxylate (7.9 g, 89percent), which was used in the next step without further purification. <n="38"/>1 H NMR (400 MHz, CDCI3) δ ppm 1.41 (s, 9H) 1.72 (m, 2H) 1.76 (m, 2H) 2.43 (s, 3 H) 3.21 (m, 2 H) 3.59 (m, 2H) 4.66 (m, 1 H) 7.31 (d, 2 H) 7.80 (d, 2 H).
83.8% With dmap; triethylamine In dichloromethane at 0 - 20℃; for 16 h; [001074] To a mixture ofN-Boc-4-hydroxy piperidine (15.0 g, 74.5 mmol), DMAP (0.30 g,2.4 mmol), and Et3N (15.6 mL, 112 mmol) in anhydrous dichloromethane (180 mL) wasadded p-toluenesulfonylchloride (17.04 g, 89.4 mmol) at 0 °C. After the addition, themixture was stirred at 20 oc for 16 h. The reaction mixture was diluted with brine (20 mL ),sodium carbonate solution (10 mL) and water (20 mL). The organic layer was separated,washed with brine (20 mL ), dried over N a2S04, and evaporated. The residue was purified byflash column chromatography on silica gel (230-400 mesh; 8 g) using a gradient solventmixture ofhexane:ethylacetate (100:5 to 50:50) for use in the next step. Yield: 22.2 g (83.8percent). 1H NMR (400 MHz, CDCh): 8 7.82 (d, 2H), 7.49 (d, 2H), 4.69 (b. s, 1H), 3.49 (b. m,2H), 3.15 (b. m, 2H), 1.70 (b. m, 2H), 1.51 (b. m, 2H), 1.38 (s, 9H).
82% at 20℃; for 14 h; A solution of te/?-butyl 4-hydroxypiperidine-1-carboxylate (10 g, 49.7mmol) and yO-methylbenzenesulfonyl chloride (11.8 g, 62.1 mmol) in pyridine (50 ml_) was allowed to stir at room temperature for 14 h. The solvent was removed in vacuo and the residue was partitioned between dichloromethane (200 ml_) and water (200 mL). The organic layer was washed with water (2 x 100 ml_), dried over sodium sulfate and concentrated in vacuo. Recrystallization from hexanes afforded 14.48 g (82percent) of the title compound as a colorless crystalline solid. 1H NMR (400 MHz, DMSO-ofe): δ 7.80-7.76 (m, 2H), 7.47- 7.43 (m, 2H), 4.67-4.61 (m, 1 H), 3.48-3.42 (m, 2H), 3.16-3.05 (m, 2H), 2.39 (s, 3H), 1.70-1.63 (m, 2H), 1.49-1.40 (m, 2H), 1.33 (s, 9H)
78% With dmap; triethylamine In dichloromethane at 0℃; for 72 h; Intermediate (xv)4-(Toluene-4-sulfonyloxy)-piperidine-1 -carboxylic acid tert-butyl ester To a solution of p-toluenesulfonylchloride (6.42 g, 33.69 mmol) in CH2CI2 (45 mL) and N,N-dimethylformamide (5 mL), chilled to 0°C, was added triethylamine (7.2 ml_, 51 .66 mmol), dimethylaminopyridine (275 mg, 2.25 mmol) and then dropwise addition of N-Boc-4-hydroxypiperidine (4.52 g, 22.46 mmol) in CH2CI2 (45 mL). The resulting mixture was stirred for 3 days and then added 1 M H3PO4 (40 mL), separated the layers and extracted with CH2CI2 (50 mL). The organic layers were combined, washed with NaHCO3 (aq) (40 mL), brine (40 mL), dried over MgSO4, filtered and concentrated to provide a crude solid which was purified by flash column chromatography (7 to 60percent EtOAc / Heptane) to provide 6.21 g (78 percent yield) of the title compound as a solid.LC RT = 3.54 min MS (ESI): 378 (M+Na)
78% With dmap; triethylamine In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 72 h; Intermediate (xi)4-(Toluene-4-sulfonyloxy)-piperidine-1 -carboxylic acid tert-butyl esterTo a solution of p-toluenesulfonylchloride (6.42 g, 33.69 mmol) in CH2CI2 (45 mL) and N,N-dimethylformamide (5 mL), chilled to 0°C, was added triethylamine (7.2 mL, 51 .66 mmol), dimethylaminopyridine (275 mg, 2.25 mmol) and then dropwise addition of N-Boc-4-hydroxypiperidine (4.52 g, 22.46 mmol) in CH2CI2 (45 mL). The resulting mixture was stirred for 3 days and then added 1 M H3PO4 (40 mL), separated the layers and extracted with CH2CI2 (50 mL). The organic layers were combined, washed with NaHCO3 (aq) (40 mL), brine (40 mL), dried over MgSO4, filtered and concentrated to provide a crude solid which was purified by flash column chromatography (7 to 60percent EtOAc / Heptane) to provide 6.21 g (78 percent yield) of the title compound as a solid.LC RT = 3.54 min MS (ESI): 378 (M+Na)
78% With dmap; triethylamine In dichloromethane at 0℃; Intermediate (vii)4-(Toluene-4-sulfonyloxy)-piperidine-1 -carboxylic acid tert-butyl esterTo a solution of p-toluenesulfonylchloride (6.42 g, 33.69 mmol) in CH2CI2 (45 mL) and N,N-dimethylformamide (5 mL), chilled to 0°C, was added triethylamine (7.2 mL, 51 .66 mmol), dimethylaminopyridine (275 mg, 2.25 mmol) and then dropwise addition of N-Boc-4-hydroxypiperidine (4.52 g, 22.46 mmol) in CH2CI2 (45 mL). Stirred the resulting mixture for 3 days and then added 1 M H3PO4 (40 mL), separated the layers and extracted with CH2CI2 (50 mL). Combined the organics, washed with NaHCO3 (aq) (40 mL), brine (40 mL), dried over MgSO , filtered and concentrated to provide a crude solid which was purified by flash column chromatography (7 to 60percent EtOAc / Heptane) to provide 6.21 g (78 percent yield) of the title compound as a solid.LCMS: LC RT = 3.54 min.; MS (ESI): 378 (M+Na).
76% With triethylamine In pyridine; water (b)
1-(Tert-Butoxycarbonyl)-4-(p-toluenesulfonyloxy)piperidine
1-(tert-Butoxycarbonyl)-4-hydroxypiperidine (4.81 g) was dissolved in pyridine (48 ml), added with p-toluenesulfonyl chloride (9.0 g) and triethylamine (6.7 ml) and stirred at room temperature for 17 hours.
The reaction mixture was added with cold water (500 ml) and stirred for 2 hours, and then the produced crystals were collected by filtration.
These crystals were purified by silica gel column chromatography (elution solvent: hexane:ethyl acetate=3:1) to obtain 6.49 g of the title compound. Yield: 76percent.
1H-NMR (CDCl3) δ (ppm); 1.43 (9H, s), 1.59 (2H, m), 1.70 (2H, m), 2.45 (3H, s), 3.25 (2H, m), 3.57 (2H, m), 4.67 (1H, m), 7.34 (2H, d, J=8 Hz), 7.79 (2H, d, J=8 Hz)
76% With triethylamine In pyridine; water (b)
1-(tert-Butoxycarbonyl)-4-(p-toluenesulfonyloxy)Piperidine
1-(tert-Butoxycarbonyl)-4-hydroxypiperidine (4.81 g) was dissolved in pyridine (48 ml), added with p-toluenesulfonyl chloride (9.0 g) and triethylamine (6.7 ml) and stirred at room temperature for 17 hours.
The reaction mixture was added with cold water (500 ml) and stirred for 2 hours, and then the produced crystals were collected by filtration.
These crystals were purified by silica gel column chromatography (elution solvent: hexane:ethyl acetate=3:1) to obtain 6.49 g of the title compound. Yield: 76percent.
1H-NMR (CDCl3); δ (ppm) 1.43 (9H, s), 1.59 (2H, m), 1.70 (2H, m), 2.45 (3H, s), 3.25 (2H, m), 3.57 (2H, m), 4.67 (1H, m), 7.34 (2H, d, J=8Hz), 7.79 (2H, d, J=8Hz)
68% With triethylamine In dichloromethane at 20℃; for 8 h; A mixture of iert-butyl 4-hydroxypiperidine-l-carboxylate (5.00g, 24.80 mmol, 1 eq), TsCl (5.70 g, 29.80 mmol, 1.2 eq) and Et3N ( 10.7 mL, 74.40 mmol, 3 eq) in 100 mL of anhydrous CH2C12 was stirred for 8 h at room temperature. The resulted mixture was washed with brine (30 mL) and water (30mL). The organic phase was dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (5: 1 (v/v) PE/EtOAc) to afford the title compound as a white solid (5.50 g, 68.00 percent). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 356.2 (M+l). [00374] Step 2) te -butyl 5,6-dihvdropyridine-l(2H)-carboxylate
68% With triethylamine In dichloromethane at 20℃; for 8 h; A mixture of tert-butyl 4-hydroxypiperidine-1-carboxylate (5.00 g, 24.80 mmol, 1 eq), TsCl (5.70 g, 29.80 mmol, 1.2 eq) and Et3N (10.7 mL, 74.40 mmol, 3 eq) in 100 mL of anhydrous CH2Cl2 was stirred for 8 h at room temperature. The resulted mixture was washed with brine (30 mL) and water (30 mL). The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (5:1 (v/v) PE/EtOAc) to afford the title compound as a white solid (5.50 g, 68.00percent). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 356.2 (M+1).
64.62% With dmap; triethylamine In dichloromethane at 20℃; To a stirred solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (2.5 g, 12.421mmol, 1.0 eq) in DCM (25 mL) was added triethyl amine (3.49 mL, 24.842 mmol, 2.0 eq),DMAP (0.151 g, 1.242 mmol, 0.1 eq) followed by para-toluenesulfonyl chloride (2.841 g,14.905 mmol, 1.2 eq). The reaction mixture was stirred at room temperature for overnight.10 After completion of the reaction (monitored by TLC), the reaction mixture was diluted withwater (30 mL) and extracted with DCM (3x30 mL). The combined organic extracts weredried over sodium sulfate, filtered and evaporated under reduced pressure. The residue waspurified by silica gel column chromatography by using 3percent methanol in DCM as an eluent toobtain the title compound (2.85 g, yield: 64.62percent) as an off-white solid. 1H NMR (300 MHz,15 CDCh): 8 ppm 7.80 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H), 4.71-4.64 (m, 1H), 3.64-3.54 (m, 2H), 3.31-3.18 (m, 2H), 2.45 (s, 3H), 1.83-1.68 (m, 4H), 1.44 (s, 9H); ESI-MS: m/z378.09 (M+Nat.
7.5 g at 20℃; for 12 h; 23.1
tert.butyl 4-(toluene-4-sulphonyloxy)-piperidine-1-carboxylate
5 g tert.butyl 4-hydroxypiperidine-1-carboxylate are placed in 15 ml of pyridine, then 4.7 g p-toluenesulphonyl chloride are added batchwise.
The reaction mixture is stirred at ambient temperature, after 12 hours poured onto ice water and the mixture obtained is stirred for a further hour at ambient temperature.
The precipitated solid is suction filtered and dried. 7.5 g product are obtained.
76.1 g at 20℃; 4-Methylbenzenesulfonyl chloride (52.1 g) was added to a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (50.0 g) in pyridine (248 mL) at room temperature.
The mixture was stirred at room temperature overnight.
After evaporation of the solvent, water and ethyl acetate were added to the residue.
The organic layer was separated, washed with 1M hydrochloric acid and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo.
The residue was triturated in diisopropyl ether at 0 C ("C" represents "degrees Celsius") to give the title compound (76.1 g).
1H NMR (300 MHz, CDCl3) delta 1.43 (9H, s), 1.57-1.88 (4H, m), 2.45 (3H, s), 3.14-3.32 (2H, m), 3.49-3.68 (2H, m), 4.61-4.73 (1H, m), 7.34 (2H, d, J=8.0 Hz), 7.80 (2H, d, J=8.3 Hz).

Reference: [1] Patent: WO2018/50771, 2018, A1, . Location in patent: Page/Page column 72
[2] Patent: WO2007/102883, 2007, A2, . Location in patent: Page/Page column 36-37
[3] Patent: WO2013/170072, 2013, A2, . Location in patent: Paragraph 001074
[4] Patent: WO2007/30366, 2007, A1, . Location in patent: Page/Page column 135
[5] Journal of Medicinal Chemistry, 2012, vol. 55, # 22, p. 9958 - 9972
[6] Tetrahedron, 1996, vol. 52, # 38, p. 12333 - 12350
[7] Patent: WO2011/143148, 2011, A1, . Location in patent: Page/Page column 36-37
[8] Patent: WO2011/143163, 2011, A1, . Location in patent: Page/Page column 30-31
[9] Patent: WO2011/143162, 2011, A1, . Location in patent: Page/Page column 25
[10] Patent: US2003/171370, 2003, A1,
[11] Patent: US2003/176693, 2003, A1,
[12] Patent: WO2013/71697, 2013, A1, . Location in patent: Paragraph 00373
[13] Patent: US2014/228361, 2014, A1, . Location in patent: Paragraph 0596-0597
[14] Patent: WO2018/29604, 2018, A1, . Location in patent: Page/Page column 58
[15] Patent: WO2008/138939, 2008, A1, . Location in patent: Page/Page column 36
[16] Patent: WO2008/150848, 2008, A1, . Location in patent: Page/Page column 97
[17] Patent: WO2009/62990, 2009, A2, . Location in patent: Page/Page column 23-24
[18] Patent: WO2005/97760, 2005, A1, . Location in patent: Page/Page column 80; 22/24
[19] Patent: WO2010/6086, 2010, A2, . Location in patent: Page/Page column 85-86
[20] Patent: WO2010/55083, 2010, A1, . Location in patent: Page/Page column 107
[21] Patent: US2011/21501, 2011, A1, . Location in patent: Page/Page column 78
[22] Patent: US2012/35143, 2012, A1,
[23] Patent: US2013/225609, 2013, A1, . Location in patent: Paragraph 0366; 0367
[24] Molecules, 2014, vol. 19, # 5, p. 6163 - 6183
[25] Patent: US2015/119412, 2015, A1, . Location in patent: Paragraph 0493; 0494
[26] Patent: WO2017/149463, 2017, A1, . Location in patent: Paragraph 00274
[27] Patent: WO2018/140809, 2018, A1, . Location in patent: Paragraph 00469
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YieldReaction ConditionsOperation in experiment
51% With pyridine In chloroform at 20℃; [003191 48A. tert-Butyl 4-(tosyloxy)piperidine-1-carboxylate: To an ice cooled solution of tert-butyl-4-hydroxy-piperdine (3.00 g, 14.9 mmol) in CHC13 (30 mL), pyridine (3.6 mL, 45 mmol) and TsC1 (5.68 g, 29.8 mmol) were added and the reactionmixture was stirred at rt overnight. The reaction mixture was diluted with CHC13, washed with 1.5 N aq. HC1 and brine, dried over Na2SO4, and concentrated. Purification via silica chromatography gave 48A (off-white solid, 2.70 g, 7.61 mmol, 51percent yield). LC-MS-Anal. Calc’d for C17H25N05S: 355.15, found [M+Na] 377.9. ‘HNMR(400 MHz, DMSO-d6) ö 7.83 (d, J=7.8 Hz, 2H), 7.49 (d, J=7.8 Hz, 2H), 4.69 (tt, J8.0, 3.8Hz, 1H), 3.49 (ddd, J=13.4, 6.5, 4.1 Hz, 2H), 3.15 (t, J9.4 Hz, 2H), 2.44 (s, 3H), 1.67 -1.75 (m, 2H), 1.45 - 1.54 (m, 2H), 1.38 (s, 9H).
Reference: [1] Patent: WO2014/78609, 2014, A1, . Location in patent: Paragraph 00319
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Reference: [1] Patent: US2003/153752, 2003, A1,
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Reference: [1] Patent: CN106883217, 2017, A, . Location in patent: Paragraph 0308; 0309; 0310; 0311
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  • [ 24424-99-5 ]
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Reference: [1] Patent: WO2013/71697, 2013, A1,
[2] Patent: US2014/228361, 2014, A1,
[3] Patent: WO2018/29604, 2018, A1,
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  • [ 5382-16-1 ]
  • [ 118811-07-7 ]
Reference: [1] Patent: WO2013/71697, 2013, A1,
[2] Patent: US2014/228361, 2014, A1,
[3] Patent: WO2018/29604, 2018, A1,
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Reference: [1] Patent: WO2018/50771, 2018, A1,
  • 8
  • [ 767-00-0 ]
  • [ 118811-07-7 ]
  • [ 333954-86-2 ]
YieldReaction ConditionsOperation in experiment
55.8% With potassium carbonate In N,N-dimethyl-formamide at 100℃; Step (i): Preparation of 4-(4-Cyano phenoxy) piperidine-l-carboxylic acid tert-butyl esterA solution of 4-hydroxy benzonitrile (15 g, 0.126 moles), potassium carbonate (28.89 g, 0.208 moles) and 4-(Toluene-4-sulfonyloxy) piperidine-l-carboxylic acid tert-butyl ester (57.62 g, 0.162 moles) in dimethylformamide (150 mL) was stirred at 100 °C while monitoring the progress of the reaction by thin layer chromatography. After completion of reaction, the reaction mass was quenched on to water (400 mL) and extracted with ethyl acetate (3 x 300 mL). The resulting ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to obtain the crude residue, which was further purified by flash chromatography using (ethyl acetate: hexane,l :9) to afford the title compound 21.25 g (Yield: 55.8 percent). - NMR (δ ppm): 1.47 (9H, s), 1.74 - 1.80 (2H, m), 1.91 - 1.96 (2H, m) 3.33 - 3.40 (2H, m), 3.66 - 3.72 (2H, m), 4.53 - 4.57 (1H, m), 6.94 - 6.96 (2H, d, J = 8.78 Hz), 7.57 - 7.59 (2H, d, J = 8.76 Hz);Mass (m/z): 303.4 (M+H)+.
55.8% With potassium carbonate In N,N-dimethyl-formamide at 100℃; Step (i):
Preparation of 4-(4-Cyano phenoxy)piperidine-1-carboxylic acid tert-butyl ester
A solution of 4-hydroxy benzonitrile (15 g, 0.126 moles), potassium carbonate (28.89 g, 0.208 moles) and 4-(Toluene-4-sulfonyloxy)piperidine-1-carboxylic acid tert-butyl ester (57.62 g, 0.162 moles) in dimethylformamide (150 mL) was stirred at 100° C. while monitoring the progress of the reaction by thin layer chromatography.
After completion of reaction, the reaction mass was quenched on to water (400 mL) and extracted with ethyl acetate (3*300 mL).
The resulting ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to obtain the crude residue, which was further purified by flash chromatography using (ethyl acetate:hexane, 1:9) to afford the title compound 21.25 g
(Yield: 55.8percent).
1H-NMR (δ ppm): 1.47 (9H, s), 1.74-1.80 (2H, m), 1.91-1.96 (2H, m) 3.33-3.40 (2H, m), 3.66-3.72 (2H, m), 4.53-4.57 (1H, m), 6.94-6.96 (2H, d, J=8.78 Hz), 7.57-7.59 (2H, d, J=8.76 Hz);
Mass (m/z): 303.4 (M+H)+.
Reference: [1] Patent: WO2012/114348, 2012, A1, . Location in patent: Page/Page column 11
[2] Patent: US2014/135304, 2014, A1, . Location in patent: Paragraph 0115-0117
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  • [ 877399-73-0 ]
YieldReaction ConditionsOperation in experiment
92% With caesium carbonate In N,N-dimethyl acetamide at 100℃; for 1 h; Inert atmosphere In a 2OmL reaction vial with a magnetic stirbar a mixture of 4-(toluene-4-sulfonyloxy)- piperidine-1 -carboxylic acid tert-butyl ester (1 .08 g; 3.04 mmol; 1 .00 eq.), 4-lodo-1 H-pyrazole (589.37 mg; 3.04 mmol; 1 .00 eq.) and cesium carbonate (1 .48 g; 4.56 mmol; 1.50 eq.) in DMA (7.00 mL) was heated at 100°C for ih under N2 atmosphere. LCMS at 1 hr showed indicated the reaction was complete. The reaction was diluted with ethyl acetate (50 mL) and washed with water (2x20 mL) and brine (1x20 mL).The organic layer was dried over Na2SO4, filtered, and concentrated to provide1 .06g (92percent) of 4-(4-lodo-pyrazol-1 -yl)-piperidine-1 -carboxylic acid tert-butyl ester as a colorless oil. MS (ES 1+): 378.
Reference: [1] Patent: WO2015/106058, 2015, A1, . Location in patent: Page/Page column 58; 59
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(S)-2-((tert-Butoxycarbonyl)amino)-3-phenylpropyl 4-methylbenzenesulfonate

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Chemical Structure| 141699-59-4

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tert-Butyl 4-((methylsulfonyl)oxy)piperidine-1-carboxylate

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Chemical Structure| 122536-69-0

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(S)-Benzyl 3-((methylsulfonyl)oxy)pyrrolidine-1-carboxylate

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Sulfonates

Chemical Structure| 139986-03-1

[ 139986-03-1 ]

(R)-tert-Butyl 3-(tosyloxy)pyrrolidine-1-carboxylate

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Chemical Structure| 166815-96-9

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tert-Butyl 4-((tosyloxy)methyl)piperidine-1-carboxylate

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(S)-2-((tert-Butoxycarbonyl)amino)-3-phenylpropyl 4-methylbenzenesulfonate

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tert-Butyl 4-((methylsulfonyl)oxy)piperidine-1-carboxylate

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(S)-Benzyl 3-((methylsulfonyl)oxy)pyrrolidine-1-carboxylate

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Aliphatic Heterocycles

Chemical Structure| 139986-03-1

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(R)-tert-Butyl 3-(tosyloxy)pyrrolidine-1-carboxylate

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tert-Butyl 4-((tosyloxy)methyl)piperidine-1-carboxylate

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Chemical Structure| 141699-59-4

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tert-Butyl 4-((methylsulfonyl)oxy)piperidine-1-carboxylate

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tert-Butyl 3-((methylsulfonyl)oxy)piperidine-1-carboxylate

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tert-Butyl 3-((methylsulfonyl)oxy)pyrrolidine-1-carboxylate

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Piperidines

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Chemical Structure| 141699-59-4

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