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Chemical Structure| 1187856-45-6 Chemical Structure| 1187856-45-6

Structure of 1187856-45-6

Chemical Structure| 1187856-45-6

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Product Details of [ 1187856-45-6 ]

CAS No. :1187856-45-6
Formula : C21H24ClNO3
M.W : 373.87
SMILES Code : O=C(OC[C@H]1CC[C@H](CO)CC1)N(C2=CC=CC=C2)C3=CC=C(Cl)C=C3

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Application In Synthesis of [ 1187856-45-6 ]

* 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.

  • Downstream synthetic route of [ 1187856-45-6 ]

[ 1187856-45-6 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 1187857-74-4 ]
  • [ 3236-48-4 ]
  • [ 1187856-45-6 ]
YieldReaction ConditionsOperation in experiment
In acetonitrile; at 40 - 70℃; for 19h;Inert atmosphere;Product distribution / selectivity; Step A: Preparation of ((lr,4r)-4-(Hydroxymethyl)cyclohexyl)methyl 4- chIorophenyI(phenyl)carbamate.A 50-liter glass-lined reactor equipped with overhead agitation, jacket temperature control, and a nitrogen atmosphere was charged with (lr,4r)-cyclohexane-l,4-diyldimethanol (3.97 kg) and acetonitrile (12.71 kg). The reactor contents were stirred at 130 rpm and heated to 63 C for 1.2 h to achieve dissolution. The mixture was cooled to < 40 C and then filtered. The filtrate was stored in a carboy. 4-Chloro-N-phenylaniline (1.60 kg), K3P04 (0.50 kg), CDI (1.41 kg) and acetonitrile (6.29 kg) were charged to a 50-liter glass-lined reactor equipped with overhead agitation, jacket temperature control, and a nitrogen atmosphere. The reactor contents were stirred at 130 rpm and heated to 65 C to 70 C for 3 h, after which conversion of 4-chloro- N-phenylaniline to N-(4-chlorophenyl)-N-phenyl-lH-imidazole-l-carboxamide was 98.0% by HPLC peak area. The reaction mixture was cooled to less than 40 C and the solution of (lr,4r)- cyclohexane-l,4-diyldimethanol in acetonitrile prepared earlier was added to the mixture. The reactor contents were stirred at 130 rpm and heated at 65 to 70 C for 19 h, after which conversion of N-(4-chlorophenyl)-N-phenyl-lH-imidazole-l-carboxamide to ((lr,4r)-4- (hydroxymethyl)cyclohexyl)methyl 4-chlorophenyl(phenyl)carbamate was verified to be 98.0% by HPLC peak area. The reactor contents were filtered and the filter cake was rinsed with acetonitrile (2.00 kg). The filtrate was transferred back to the reactor and most of the acetonitrile (18.48 kg) was then removed at 22 C by vacuum distillation at 80 mm Hg. Water (5.34 kg) was added to the reactor and 1.55 kg of water/acetonitrile mixture was then removed by vacuum distillation at 29 C and 70 mm Hg. Water (5.34 kg) was added to the reactor and the product precipitated during the addition. The resulting mixture was stirred at 20 C to 25 C for 13 h. The precipitated product was filtered and washed with aqueous acetonitrile in two portions (1.59 kg acetonitrile dissolved in 6.00 kg water). The product was dried under reduced pressure at < 60C (until loss-on-drying was < 2 wt%) to give the title compound as an off-while solid (2.29 kg, 78% yield; 97% purity by HPLC peak area.)
In acetonitrile; at 65℃;Inert atmosphere;Product distribution / selectivity; Example 1.106: Preparation of Sodium 2-(((lr,4r)-4-(((4- Chlorophenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)methoxy)acetate.; Method 1.; Step A: Preparation of ((lr,4r)-4-(hydroxymethyl)cyciohexyI)methyl 4- chlorophenyl(phenyl)carbamate.; 4-Chloro-N-phenylaniline (15.0 g, 73.6 mmol), tribasic potassium phosphate, (fine powder, 4.69 g, 22.1 mmol), N^V-carbonyldiimidazole (13.14 g, 81 mmol) and acetonitrile (75 mL) were charged to a 500-mL, jacketed, four-necked cylindrical reaction flask equipped with a mechanical stirrer and a condenser. The reaction mixture was heated at 65 0C under nitrogen and monitored by HPLC. After about 2.5 h HPLC showed > 98% conversion to the intermediate <n="169"/>N-(4-chlorophenyl)-N-phenyl-lH-imidazole-l-carboxamide. After about 5.5 h a solution of (lr,4r)-cyclohexane-l,4-diyldimethanol (37.2 g, 258 mmol) in acetonitrile (150 mL) at 65 0C was added to the reaction mixture over 20 min. The resulting mixture was heated at 65 0C overnight. etaPLC showed about 98% conversion to the required product. The mixture was filtered, and the cake was rinsed with acetonitrile (2 x 25 mL). The filtrate was concentrated under reduced pressure (40 0C, 32 torr) 124.125 g of distillate was collected. The residue was diluted with water (50 mL) and this mixture was concentrated under reduced pressure (400C, 32 torr) and 35.184 g of distillate was collected. The residue was diluted with water (50 mL) and the resulting mixture was allowed to stir overnight to give a white paste. The mixture was filtered, and the cake was rinsed with 25% acetonitrile/water (2 x 75 mL). The solid was dried in a vacuum oven to leave a white solid (22.271 g); 94.8% purity by etaPLC peak area. LCMS m/z = 374.3 [M+eta]+; 1H nuMR (400 MHz, DMSO-^6) delta ppm 0.77 - 0.93 (m, 4 H) 1.23 (dd, J = 6.22, 3.51 Hz, 1 H) 1.47 (dd, J = 6.32, 2.91 Hz, 1 H) 1.56 - 1.76 (m, 4 H) 3.20 (t, J= 5.78 Hz, 2 H) 3.92 (d, J = 6.13 Hz, 2 H) 4.33 (t, J = 5.31 Hz, 1 H) 7.28 - 7.35 (m, 5 H) 7.38 - 7.47 (m, 4 H).
  • 2
  • [ 1187856-44-5 ]
  • [ 3236-48-4 ]
  • [ 1187856-45-6 ]
YieldReaction ConditionsOperation in experiment
57% With pyridine;Sealed tube; Reflux; The carbamic chloride 2 (0.2 g, 0.75 mmol) and (1 r,4r)-cyclohexane-1 ,4-diyldimethanol (0.12 g, 0.83 mmol) were dissolved in pyridine (0.81 ml.) in a sealed tube. The reaction mixture was heated overnight under reflux. After cooling, the mixture was partitioned between 1 M HCI and EtOAc. The aq. layer was extracted with EtOAc and the combined organic extracts were washed with brine, dried over MgS04, and concentrated. The crude was purified via column chromatography eluting with 2-5% MeOH/DCM to yield 0.16 g (57%) of the title compound as a light peach colored solid. 1 H NMR (400 MHz, Chloroform- ) d 7.33 (t, J = 7.6 Hz, 2H), 7.30 - 7.26 (m, 2H), 7.24 - 7.14 (m, 5H), 3.97 (d, J = 6.2 Hz, 2H), 3.43 (t, J = 5.7 Hz, 2H), 1 .78 (d, J = 7.9 Hz, 2H), 1 .67 (d, J = 7.7 Hz, 2H), 1 .36 (d, J = 1 1.7 Hz, 1 H), 1.23 (t, J = 5.8 Hz, 1 H), 0.93 (q, J = 1 1.4, 10.5 Hz, 4H).
With pyridine;Reflux; Step B: Preparation of ((lr,4r)-4-(Hydroxymethyl)cyclohexyl)methyl 4- chlorophenyl(phenyl)carbamate.; 4-Chlorophenyl(phenyl)carbamic chloride (12.34 g, 46.4 mmol) and (lr,4r)- cyclohexane-l,4-diyldimethanol (6.69 g, 46.4 mmol) were dissolved in pyridine (50 mL, 618 mmol). The reaction mixture was heated to reflux overnight, cooled and concentrated under reduced pressure. The residue was resuspended in Et2O/EtOAc (50:50), filtered and washed with EtOAc and Et2O. The filtrate was extracted with 1 M HCl (200 mL) and EtOAc (200 mL). The aqueous layer was extracted again with EtOAc (100 mL). The organic layers were combined and washed with H2O (200 mL), dried, and concentrated. The residue was purified by silica gel column chromatography to provide the title compound as a light pink colored solid (10.4 g). LCMS m/z = 374.1 [M+H]+; 1H nuMR (400 MHz, DMSO-^6) delta ppm 0.73-0.92 (m, 4H), 1.13-1.27 (m, IH), 1.36-1.50 (m, IH), 1.53-1.62 (m, 2H), 1.62-1.73 (m, 2H), 3.17 (d, J= 6.19 Hz, 2H), 3.89 (d, J = 6.06 Hz, 2H), 4.29 (bs, IH), 7.23-7.32 (m, 5H), 7.34-7.45 (m, 4H).
 

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