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Chemical Structure| 72351-36-1

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Product Details of [ 72351-36-1 ]

CAS No. :72351-36-1
Formula : C17H19NO
M.W : 253.34
SMILES Code : OCC1CN(C(C2=CC=CC=C2)C3=CC=CC=C3)C1
MDL No. :MFCD03407522
InChI Key :GEFUGGQLCNKIQP-UHFFFAOYSA-N
Pubchem ID :2758715

Safety of [ 72351-36-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P233-P260-P261-P264-P271-P280-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P332+P313-P337+P313-P340-P362-P403-P403+P233-P405-P501

Application In Synthesis of [ 72351-36-1 ]

* 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 [ 72351-36-1 ]

[ 72351-36-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 36476-87-6 ]
  • [ 72351-36-1 ]
YieldReaction ConditionsOperation in experiment
54% 1-Benzhydryl-3-azetidinecarboxylic acid (3.12 g) was suspended in tetrahydrofuran (60 ml), and cooled in an ice-methanol bath under a nitrogen atmosphere. Triethylamine (1.96 ml) was added dropwise, and a solution of ethyl chlorocarbonate (1.34 ml) in tetrahydrofuran (5 ml) was added dropwise over 20 minutes. After the addition, the reaction mixture was stirred at the same temperature for 30 minutes. The reaction mixture was filtered, and the residue was washed with tetrahydrofuran (30 ml). The filtrate was added dropwise to a solution of an aqueous (15 ml) solution of sodium borohydride (1.33 g) cooled in an ice water bath over 15 minutes. After the addition, the reaction mixture was stirred at room temperature. 1N hydrochloric acid (35 ml) was gradually added to the reaction mixture to degrade excess sodium borohydride, and a 1N aqueous solution of sodium hydroxide (35 ml) was added. This was extracted with ethyl acetate (100 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated, and the residue was dried under reduced pressure to give the title compound (1.59 g, 54%) as a pale brown solid.1H-NMR Spectrum (CDCl3) δ (ppm): 2.57 (1H, m), 3.03 (2H, m), 3.24 (2H, m), 3.80 (2H, d, J=5.2 Hz), 4.33 (1H, s), 7.15-7.45 (10H, m).ESI-MS (m/z): 254[M+H]+.
54% (Reference Example F-4) 1-Benzhydryl-3-(hydroxymethyl)azetidine 1-Benzhydryl-3-azetidinecarboxylic acid (3.12 g) was suspended in tetrahydrofuran (60 ml) and cooled under a nitrogen atmosphere in an ice-ethanol bath. Triethylamine (1.96 ml) was added dropwise, and a solution of ethyl chlorocarbonate (1.34 ml) in tetrahydrofuran (5 ml) was added dropwise over 20 min. After the dropwise addition, stirring was carried out at the same temperature for 30 min. The reaction mixture was filtered and washed with tetrahydrofuran (30 ml). The filtrate was added dropwise over 15 min to an aqueous (15 ml) solution of sodium borohydride (1.33 g) cooled in an ice water bath. Upon completion of the dropwise addition, the reaction mixture was stirred at room temperature. To the reaction mixture was gradually added 1N hydrochloric acid (35 ml) to decompose excess sodium borohydride, and a 1N aqueous solution of sodium hydroxide (35 ml) was added. This was extracted with ethyl acetate (100 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated, and the residue was dried under reduced pressure to provide the titled compound as a pale brown solid (1.59 g, 54 %). 1H-NMR Spectrum (CDCl3) δ (ppm): 2.57 (1H, m), 3.03 (2H, m), 3.24 (2H, m), 3.80 (2H, d, J = 5.2 Hz), 4.33 (1H, s), 7.15-7.45 (10H, m). ESI-MS (m/z):254[M+H]+.
54% (Production Example 102) 1-Benzhydryl-3-(hydroxymethyl)azetidine 1-Benzhydryl-3-azetidinecarboxylic acid (3.12 g) was suspended in tetrahydrofuran (60 ml) and cooled under a nitrogen atmosphere in an ice-ethanol bath. Triethylamine (1.96 ml) was added dropwise, and a solution of ethyl chlorocarbonate (1.34 ml) in tetrahydrofuran (5 ml) was added dropwise over 20 min. After the dropwise addition, stirring was carried out at the same temperature for 30 min. The reaction mixture was filtered and washed with tetrahydrofuran (30 ml). The filtrate was added dropwise over 15 min to an aqueous (15 ml) solution of sodium borohydride (1.33 g) cooled in an ice water bath. Upon completion of the dropwise addition, the reaction mixture was stirred at room temperature. To the reaction mixture was gradually added 1N hydrochloric acid (35 ml) to decompose excess sodium borohydride, and a 1N aqueous solution of sodium hydroxide (35 ml) was added. This was extracted with ethyl acetate (100 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated, and the residue was dried under reduced pressure to provide the titled compound as a pale brown solid (1.59 g, 54 %). 1H-NMR Spectrum (CDCl3) δ (ppm): 2.57 (1H, m), 3.03 (2H, m), 3.24 (2H, m), 3.80 (2H, d, J = 5.2 Hz), 4.33 (1H, s), 7.15-7.45 (10H, m). ESI-MS (m/z):254[M+H]+.
65.1. (1 -Benzhydryl-azetidin-3-yl)-methanol: l-Benzhydrylazetane-3-carboxylic acid (101 mg) was dissolved in THF (2 mL) and lithium aluminium hydride (27 mg) was added. The mixture was stirred overnight at RT. Water, sodium potassium tartrate solution and EA were added. The phases were separated, the org. phase was dried (Na2SO4) and evaporated off to afford 93 mg of the desired product. LC-MS (A): tR = 0.67 min; [M+H]+: 254.16.
With lithium aluminium tetrahydride; In tetrahydrofuran;Heating / reflux; A solution of 1-(diphenylmethyl)-3-(hydroxymethyl) azetidine (1 g, 3.9 mmol) [prepared by reduction of 1-(diphenylmethyl)azetidine-3-carboxylic acid (CAS No.: 36476-87-6) using LiAlH4 in refluxing THF] and Et3N (0.71 mL, 5.1 mmol) in THF (30 mL) was treated with methanesulfonyl chloride (0.36 mL, 4.7 mmol) and stirred for 2 h at room temperature. The precipitate was removed by filtration and washed with THF. The liquors were evaporated and the residue partitioned between water and DCM. The DCM layer was separated and the aqueous re-extracted. The combined organics were washed with brine, dried (Na2SO4), filtered and evaporated. The residue was triturated with isohexane, the solid then isolated by filtration and dried to give the title compound as an orange solid (1.1g, 84%). m/z (ES+) 332 (M+H)+.

  • 2
  • [ 72351-36-1 ]
  • [ 1354961-13-9 ]
  • tert-butyl 4-((1-benzhydrylazetidin-3-yl)methoxy)-5-chloro-2-fluorobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With potassium tert-butylate; In dimethyl sulfoxide; at 20℃; for 1h; To solution of (1-benzhydrylazetidin-3-yl) methanol (1.141 g) and tert-butyl 5-chloro-2, 4-difluoro-benzoate (1.244 g, 90 pure) in DMSO (13.5 mL) at 14 (bath) was added potassium tert-butoxide (0.606 g) . The mixture was stirred at rt for 1 hr. Diluted with EtOAc, the contents were washed with dilute NaHCO3 (2x) and brine (1x) , and dried (Na2SO4) . After filtration and concentration, the crude was purified with silica gel flash chromatography (0-40EtOAc/heptane) to give the product (1.359 g, 63) .
 

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