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[ CAS No. 88157-42-0 ] {[proInfo.proName]}

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Chemical Structure| 88157-42-0
Chemical Structure| 88157-42-0
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Product Details of [ 88157-42-0 ]

CAS No. :88157-42-0 MDL No. :MFCD16036399
Formula : C6H10O3 Boiling Point : -
Linear Structure Formula :- InChI Key :YLNAXTUVFOXHTI-UHFFFAOYSA-N
M.W : 130.14 Pubchem ID :22934721
Synonyms :

Calculated chemistry of [ 88157-42-0 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.83
Num. rotatable bonds : 3
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 31.03
TPSA : 46.53 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.3 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.58
Log Po/w (XLOGP3) : -0.29
Log Po/w (WLOGP) : -0.13
Log Po/w (MLOGP) : 0.0
Log Po/w (SILICOS-IT) : 0.74
Consensus Log Po/w : 0.38

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.27
Solubility : 70.5 mg/ml ; 0.542 mol/l
Class : Very soluble
Log S (Ali) : -0.23
Solubility : 77.1 mg/ml ; 0.592 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.57
Solubility : 35.2 mg/ml ; 0.27 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.43

Safety of [ 88157-42-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 88157-42-0 ]

* 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 [ 88157-42-0 ]

[ 88157-42-0 ] Synthesis Path-Downstream   1~50

  • 1
  • [ 88157-42-0 ]
  • [ 43161-30-4 ]
YieldReaction ConditionsOperation in experiment
90% With carbon tetrabromide; triphenylphosphine In dichloromethane at 0℃;
With carbon tetrabromide; triphenylphosphine In dichloromethane at 20℃; for 0.0333333h; 163 To a solution of the compound obtained in Referential Example 162 (4.20 g) in methylene chloride (168 mL) were added triphenylphosphine (10 g) and carbon tetrabromide (16 g) at room temperature under nitrogen atmosphere, and after 2 minutes, saturated aqueous sodium hydrogencarbonate was added thereto. The organic layer was washed with saturated brine, and was dried over sodium sulfate anhydrate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate : hexane = 1:19), to thereby give the title compound (2.15 g).1H-NMR(CDCl3) δ:1.00-1.05(2H, m), 1.52-1.59(2H, m), 3.61(2H, s), 3.73(3H, s).
With carbon tetrabromide; triphenylphosphine In dichloromethane at 20℃; for 0.0333333h; 163 methyl 1-(bromomethyl)cyclopropanecarboxylate: [Referential Example 163] methyl 1-(bromomethyl)cyclopropanecarboxylate: triphenylphosphine (10 g) and carbon tetrabromide (16 g) were added to a solution of the compound (4.20 g) obtained in Referential Example 162 in methylene chloride (168 ml) at room temperature under a nitrogen atmosphere.. After 2 minutes, a saturated aqueous solution of sodium hydrogencarbonate was added thereto.. After the resultant organic layer was washed with saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure.. The resultant residue was purified by column chromatography on silica gel (ethyl acetate:hexane = 1:19) to obtain the title compound (2.15 g).1H-NMR (CDCl3) δ: 1.00-1.05(2H,m), 1.52-1.59(2H,m), 3.61(2H,s), 3.73(3H,s).
  • 2
  • [ 88157-41-9 ]
  • [ 88157-42-0 ]
YieldReaction ConditionsOperation in experiment
75% With sodium tetrahydroborate In methanol at -35℃;
  • 3
  • [ 88157-42-0 ]
  • (1-{(Z)-2-[((Z)-1-Hept-1-enyl)-cyclopropyl]-vinyl}-cyclopropyl)-methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) DME-HMPA, -30 to 25 deg C 4: DIBAL / CH2Cl2 / -78 °C
  • 4
  • [ 88157-42-0 ]
  • [ 88157-26-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) DME-HMPA, -30 to 25 deg C 4: DIBAL / CH2Cl2 / -78 °C 5: SO3/pyr, Et3N / dimethylsulfoxide / 25 °C
  • 5
  • [ 88157-42-0 ]
  • [ 88157-22-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) DME-HMPA, -30 to 25 deg C 4: 94 percent / DIBAL / CH2Cl2 / -78 °C 5: SO3/pyr, Et3N / dimethylsulfoxide / 25 °C
  • 6
  • [ 88157-42-0 ]
  • [ 88157-50-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) DME-HMPA, -30 to 25 deg C 4: 94 percent / DIBAL / CH2Cl2 / -78 °C
  • 7
  • [ 88157-42-0 ]
  • 1-{(Z)-2-[((Z)-1-Hept-1-enyl)-cyclopropyl]-vinyl}-cyclopropanecarboxylic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) DME-HMPA, -30 to 25 deg C
  • 8
  • [ 88157-42-0 ]
  • [ 88157-47-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) THF-HMPA, -30 to 25 deg C 4: DIBAL / CH2Cl2 / 0 °C
  • 9
  • [ 88157-42-0 ]
  • [ 88157-40-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) THF-HMPA, -30 to 25 deg C 4: DIBAL / CH2Cl2 / 0 °C 5: SO3/pyr, Et3N / dimethylsulfoxide / 25 °C
  • 10
  • [ 88157-42-0 ]
  • 1-{(Z)-2-[((1Z,4Z)-1-Deca-1,4-dienyl)-cyclopropyl]-vinyl}-cyclopropanecarboxylic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) DME-HMPA, -30 to 25 deg C
  • 11
  • [ 88157-42-0 ]
  • [ 88157-15-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) DME-HMPA, -30 to 25 deg C 4: DIBAL / CH2Cl2 / -78 °C 5: SO3/pyr, Et3N / dimethylsulfoxide / 25 °C 6: 1.) NaN(SiMe3)2 / 1.) HMPA, 25 deg C
  • 12
  • [ 88157-42-0 ]
  • 1-[(Z)-2-(1-{(Z)-2-[((Z)-1-Hept-1-enyl)-cyclopropyl]-vinyl}-cyclopropyl)-vinyl]-cyclopropanecarboxylic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) THF-HMPA, -30 to 25 deg C
  • 13
  • [ 88157-42-0 ]
  • [ 88157-14-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) DME-HMPA, -30 to 25 deg C 4: 94 percent / DIBAL / CH2Cl2 / -78 °C 5: SO3/pyr, Et3N / dimethylsulfoxide / 25 °C 6: 1.) NaN(SiMe3)2 / 1.) DME, 0 deg C
  • 14
  • [ 88157-42-0 ]
  • [ 88157-17-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C 3: 1.) NaN(SiMe3)2 / 1.) THF-HMPA, -30 to 25 deg C 4: DIBAL / CH2Cl2 / 0 °C 5: SO3/pyr, Et3N / dimethylsulfoxide / 25 °C 6: 1.) NaN(SiMe3)2 / 1.) DME, 0 deg C
  • 15
  • [ 88157-42-0 ]
  • [ 88157-19-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 90 percent / CBr4, Ph3P / CH2Cl2 / 0 °C 2: 90 percent / acetonitrile / 65 °C
  • 16
  • [ 113020-21-6 ]
  • [ 88157-42-0 ]
YieldReaction ConditionsOperation in experiment
91% Preparation 21Methyl 1 -(hydroxymeth l)cyclopropanecarboxylate1-Methoxycarbonylcyclopropane carboxylic acid (16.4 g, 1 13.89 mmol), TEA (17.6 mL, 127.55 mmol), and THF (325 mL) are charged in a round bottom flask. The mixture is cooled to -10 C and isobutyl chloroformate (16.5 mL, 127.55 mmol) is added dropwise. The solution is stirred for 1 h. In a separate flask, sodium borohydride (13 g, 341.67 mmol) is dissolved in a mixture of THF (165 mL) and water (40 mL) and cooled in an ice bath. The insoluble material is removed by filtration from the first solution. To the borohydride solution is added the 1- methoxycarbonylcyclopropane carboxylic acid solution described above, dropwise over a period of 1.5 h. The resulting solution is stirred at the same temperature for 1 h. The reaction mixture is poured into a cooled 20% aqueous solution of citric acid and extracted with ethyl acetate (3 x 150 mL). The combined organic layers are washed with brine, dried over MgS04, filtered, and concentrated under reduced pressure to afford the title compound (13.5 g, 91%). ¾ NMR(400 MHz, CDC13); delta 0.9-0.8 (m, 2H), 1.3-1.2 (m, 2H), 3.62 (s, 2H) 3.69 (s, 3H).
77% At -10 C, Isobutyl chloroformate (10.2 mL, 78 mmol) Add dropwise to <strong>[113020-21-6]1,1-cyclopropyldicarboxylic acid monomethyl ester</strong> (10.0 g, 69.4 mmol) And triethylamine (10.8 mL, 78 mmol) In a solution of tetrahydrofuran (200 mL), And stirred at this temperature for 1 hour. Then the reaction system is warmed to 0 C, Filter out the solids in the reaction solution, The filtrate is ready for use. Sodium borohydride (7.87 g, 208 mmol) under ice bath Tetrahydrofuran (100mL) a mixed solution with water (25 mL) was added dropwise to the above filtrate. Adding time 1 hour, Plus, The resulting reaction solution was further stirred under ice bath for 1 hour. Pour the reaction solution into a 20% aqueous solution of citric acid. Stir for 5 minutes, Concentrate to remove the organic solution, The aqueous phase was extracted with ethyl acetate. Organic phase merger, Wash with water and saturated salt in turn, Dry over anhydrous sodium sulfate, filter, Concentration gave Compound 19.1 (6.9 g, yield: 77%) as an oily liquid.
The compound obtained in Referential Example 161 (9.0 g) and triethylamine (9.7 mL) were dissolved in tetrahydrofuran (180 mL). After the solution was cooled to - 10C, isobutyl chloroformate (9.1 mL) was added dropwise thereto, followed by stirring for 1 hour. Sodium borohydride (7.1 g) was dissolved in a mixture of tetrahydrofuran (100 mL) and water (25 mL). After this solution was cooled under ice cooling, the previously prepared solution was added dropwise thereto while insoluble matter was removed by filtration, and the thus-obtained mixture was stirred at the same temperature for 1 hour. The reaction mixture was poured into a chilled 10% aqueous citric acid, and the thus-obtained mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and was dried over sodium sulfate anhydrate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate : hexane = 1:9 to 2:1), to thereby give the title compound (4.25 g).1H-NMR(CDCl3) delta:0.87-0.93(2H, m), 1.28-1.30(2H, m), 3.63(2H, s), 3.70(3H, s).
The above product was mixed with DIPEA (1.2 eq) in THF and stirred at 0 C. for 10 minutes, to the reaction was added ethyl chloroformate (1 eq) slowly and further stirred for 1.5 hours from 0 C. to RT. To the reaction cooled at 0 C. was added NaBH4 (1.5 eq) slowly followed by MeOH (2 eq) and stirred for 2 hours from 0 C. to RT. The reaction was diluted with EtOAc, water and extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried. The solution was evaporated and purified with silica gel column to give methyl 1-(hydroxymethyl)cyclo-propanecarboxylate (2.5 g).
[Referential Example 162] methyl 1-(hydroxymethyl)cyclopropanecarboxylate: The compound (9.0 g) obtained in Referential Example 161 and triethylamine (9.7 ml) were dissolved in tetrahydrofuran (180 ml), and the solution was cooled to -10C, to which isobutyl chloroformate (9.1 ml) was added dropwise, and the resultant mixture was stirred for 1 hour.. On the other hand, sodium borohydride (7.1 g) was dissolved in tetrahydrofuran (100 ml)-water (25 ml) and cooled with ice.. While removing insoluble matter by filtration, the solution prepared previously was added dropwise, and the resultant mixture was stirred at the same temperature for 1 hour.. The reaction mixture was poured into a cooled 10% aqueous solution of citric acid to conduct extraction with ethyl acetate.. After the extract was washed with saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure.. The resultant residue was purified by column chromatography on silica gel (ethyl acetate:hexane = 1:9 - 2:1) to obtain the title compound (4.25 g).1H-NMR (CDCl3) delta: 0.87-0.93(2H,m), 1.28-1.30(2H,m), 3.63(2H,s), 3.70(3H,s).
The above product was mixed with DIPEA (1.2 eq) in THF and stirred at 0 C. for 10 minutes, to the reaction was added ethyl chloroformate (1 eq) slowly and further stirred for 1.5 hours from 0 C. to RT. To the reaction cooled at 0 C. was added NaBH4 (1.5 eq) slowly followed by MeOH (2 eq) and stirred for 2 hours from 0 C. to RT. The reaction was diluted with EtOAc, water and extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried. The solution was evaporated and purified with silica gel column to give methyl 1-(hydroxymethyl)cyclo-propanecarboxylate (2.5 g).
1 , 1 -Cyclopropane dicarboxylic acid-l-methyl ester (4 g, 27.8 mmol) was mixed with DIPEA (6 ml, 34.4 mmol) in THF (50 ml) and stirred at a 0 C for 10 min. To the reaction was slowly added ethyl chloroformate (2.7 ml, 28.1 mmol). The reaction was stirred for 1.5 hours and allowed to warm to ambient temperature. The reaction was then re-cooled to 0 C and NaBH4 (1.6 g, 42.3 mmol) was slowly added, followed by the addition of methanol (3 ml, 74.2 mmol). The reaction was allowed to warm to ambient temperature2 h. Then the reaction was diluted with EtOAc and water. The aqueous layer was separated and extracted with EtOAc three times. The combined organic layers were washed with water, then brine, dried(MgS04), filtered, and concentrated to afford the title compound.lH NMR (500 MHz, CDClj): delta 3.70 (s, 3H), 3.60 (s, 2H), 1.25 (m, 2H), 0.85 (m, 2H).

  • 17
  • [ 558-13-4 ]
  • [ 88157-42-0 ]
  • [ 43161-30-4 ]
YieldReaction ConditionsOperation in experiment
With sodium chloride; sodium hydrogencarbonate; triphenylphosphine In dichloromethane R.163 Methyl 1-(bromomethyl)cyclopropanecarboxylate: REFERENTIAL EXAMPLE 163 Methyl 1-(bromomethyl)cyclopropanecarboxylate: Triphenylphosphine (10 g) and carbon tetrabromide (16 g) were added to a solution of the compound (4.20 g) obtained in Referential Example 162 in methylene chloride (168 ml) at room temperature under a nitrogen atmosphere. After 2 minutes, a saturated aqueous solution of sodium hydrogencarbonate was added thereto. After the resultant organic layer was washed with saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:19) to obtain the title compound (2.15 g). 1H-NMR (CDCl3) δ: 1.00-1.05(2H,m), 1.52-1.59(2H,m), 3.61(2H,s), 3.73(3H,s).
  • 18
  • [ 113020-21-6 ]
  • [ 543-27-1 ]
  • [ 88157-42-0 ]
YieldReaction ConditionsOperation in experiment
100% Example 164A methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate A solution of <strong>[113020-21-6]1-(methoxycarbonyl)cyclopropanecarboxylic acid</strong> (10 g, 69.4 mmol) and triethylamine (10.83 ml, 78 mmol) in tetrahydrofuran (200 mL) under N2 was cooled to -10 C., treated with isobutyl chloroformate (10.21 mL, 78 mmol) dropwise and stirred at -10 C. for 1 hour. The mixture was warmed to 0 C. and the solid was removed by filtration. In a separate flask, NaBH4 (7.87 g, 208 mmol) was dissolved in a mixture of tetrahydrofuran (100 mL) and water (25 mL). This mixture was then cooled to 0 C. and added dropwise to the filtrate over 90 minutes. Stirring was continued for 1 hour at 0 C. and the mixture was poured into a 0 C. solution of 20% citric acid in water. The mixture was swirled for 5 minutes and then concentrated on the rotory evaporator with minimal heating to remove the majority of the tetrahydrofuran. The residue was extracted with ethyl acetate (4*150 mL). The combined ethyl acetate layers were washed with brine, dried (MgSO4), filtered, and concentrated to provide the title compound (9 g, 69.2 mmol, 100% yield). 1H NMR (500 MHz, CDCl3) delta 4.44 (bs, 1H), 3.68 (s, 3H), 3.62 (s, 2H), 1.27-1.25 (m, 2H), 0.88-0.86 (m, 2H).
With sodium borohydrid; sodium chloride; triethylamine; citric acid; In tetrahydrofuran; tetrahydrofuran (100 ml)-water; REFERENTIAL EXAMPLE 162 Methyl 1-(hydroxymethyl)cyclopropanecarboxylate: The compound (9.0 g) obtained in Referential Example 161 and triethylamine (9.7 ml) were dissolved in tetrahydrofuran (180 ml), and the solution was cooled to -10 C., to which isobutyl chloroformate (9.1 ml) was added dropwise, and the resultant mixture was stirred for 1 hour. On the other hand, sodium borohydride (7.1 g) was dissolved in tetrahydrofuran (100 ml)-water (25 ml) and cooled with ice. While removing insoluble matter by filtration, the solution prepared previously was added dropwise, and the resultant mixture was stirred at the same temperature for 1 hour. The reaction mixture was poured into a cooled 10% aqueous solution of citric acid to conduct extraction with ethyl acetate. After the extract was washed with saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was purified by column chromatography on silica gel (ethyl acetate:hexane=1:9-2:1) to obtain the title compound (4.25 g). 1H-NMR (CDCl3) delta: 0.87-0.93(2H,m), 1.28-1.30(2H,m), 3.63(2H,s), 3.70(3H,s).
  • 19
  • [ 88157-42-0 ]
  • [ 498-02-2 ]
  • [ 1058137-71-5 ]
YieldReaction ConditionsOperation in experiment
Stage #1: methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With methanesulfonyl chloride In dichloromethane for 0.5h; Stage #3: 1-(3-methoxy-4-hydroxyphenyl)ethanone With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 6h; 1.C The above product was dissolved into DCM (40 ml) with DIPEA (4 ml) and stirred at 0° C. for 15 minutes. To the reaction was added MsCl (1.1 eq) and stirred for 30 minutes. The reaction was washed with NaHCO3 solution, water, brine and dried with Na2SO4. The solution was evaporated and mixed with 4-hydroxy-3-methoxy-acetophenone (0.9 eq) and K2CO3 (1.5 eq) in DMF (20 ml). The reaction was heated at 100° C. for 6 hours and diluted with EtOAc, water and extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried further evaporated to give methyl 1-((4-acetyl-2-methoxyphenoxy)methyl)cyclopropane-carboxylate (1.8 g). This product was dissolved into acetic acid (5 ml) and stirred at RT, to the reaction was very slowly added nitric acid (8 ml, 60%) and stirred at RT for 1 hour. The reaction was poured into ice-water and extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried.
  • 20
  • [ 124-63-0 ]
  • [ 88157-42-0 ]
  • C7H12O5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine In dichloromethane at 30℃; for 3h; Cooling with ice; 26.2 Step 2 Under ice bath conditions,Methanesulfonyl chloride (7.4 g, 64.5 mmol)Add dropwise to compound 19.1 (5.6 g, 43 mmol)And triethylamine (8.7 mL, 86 mmol)In a solution of dichloromethane (100 mL),Stir at room temperature for 3 hours.The reaction solution was diluted with dichloromethane.Hydrochloric acid (1.0M),Wash with water and saturated brine,The organic phase is dried over anhydrous sodium sulfate.filter,Concentration gave Compound 19.2 (8.9 g, yield: 100%) as a white solid.
Stage #1: methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.25h; Stage #2: methanesulfonyl chloride In dichloromethane for 0.5h; 9 The above product was dissolved into DCM (40 ml) with DIPEA (4 ml) and stirred at O° C. for 15 minutes. To the reaction was added MsCl (1.1 eq) and stirred for 30 minutes. The reaction was washed with NaHCO3 solution, water, brine and dried with Na2SO4. The solution was evaporated and mixed with 4-hydroxy-3-methoxy-acetophenone (0.9 eq) and K2CO3 (1.5 eq) in DMF (20 ml). The reaction was heated at 100° C. for 6 hours and diluted with EtOAc, water and extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried further evaporated to give methyl 1-((4-acetyl-2-methoxyphenoxy)methyl)-cyclopropane-carboxylate (1.8 g). This product was dissolved into acetic acid (5 ml) and stirred at RT, to the reaction was very slowly added nitric acid (8 ml, 60%) and stirred at RT for 1 hour. The reaction was poured into ice-water and extracted with EtOAc three times. The combined organic layer was washed with water, brine and dried.
  • 21
  • [ 1332706-87-2 ]
  • [ 88157-42-0 ]
  • [ 1332707-02-4 ]
YieldReaction ConditionsOperation in experiment
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 80℃; 13.A To a solution of 5-(biphenyl-4-yI)-6-ch{oro-2- (methylsulfonyl)-l-tprop-2-en-l-yl)-lH-benzimida2ole (Intermediate 4, 150 mg, 0.355 mmol) and methyl- l-(hydroxymethyl)cyclopropane carboxylate (Intermediate 11, 70 mg, 0.538 mmol) in DMF (2 ml) was added DBU (0.27 ml, 1.791 mmol) dropwise. The reaction mixture was stirred overnight at 80 °C. The volatiles were removed in vacuo and the resulting residue partitioned between EtOAc and ¾0. The aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried (MgS04), filtered, and concentrated. Chromatography of the resulting residue over silica (preparative TLC) eluting with 35%EtOAc/hexanes afforded the desired product. LC-MS: calculated for C28H25C1N203 472.16, observed m/e: 472.89 (M+H)+ (Rt 2.66/4 min).
  • 22
  • [ 1332706-87-2 ]
  • [ 88157-42-0 ]
  • [ 1332706-74-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 80 °C 2.1: 1,3-dimethylbarbituric acid / tetrakis(triphenylphosphine) palladium(0) / ethanol / 15 h / 70 °C / Inert atmosphere 2.2: 1 h / 20 °C
  • 23
  • [ 6914-71-2 ]
  • [ 88157-42-0 ]
YieldReaction ConditionsOperation in experiment
60% With lithium tri-(tert-butoxy)aluminum hydride; In tetrahydrofuran; at 65℃; To a solution of dimethyl cyclopropane-1,1-dicarboxylate (6.32 g, 40 mmol) inanhydrous THF (120 mL) was added a solution of lithium tri-tert-butoxyaluminum hydride inTHF (IM, 88 mL) and the mixture was stirred at 65 °C overnight. To the mixture were addedH20 (4 mL) and 15percent aq NaOH (4 mL). The mixture was dried over drying agent and filtered.The filtrate was concentrated under reduced pressure to afford methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate as a yellow oil (3.11 g, 60percent).
  • 24
  • [ 88157-42-0 ]
  • [ 88157-41-9 ]
YieldReaction ConditionsOperation in experiment
99% With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid In dichloromethane at -5 - 20℃; for 0.416667h; Inert atmosphere; 164.164B Example 164B
methyl 1-formylcyclopropane-1-carboxylate Example 164B methyl 1-formylcyclopropane-1-carboxylate A solution of Example 164A (9.03 g, 69.4 mmol) in CH2Cl2 (180 mL) under N2 was cooled to -5° C. and treated portion wise over 20 minutes with trichloroisocyanuric acid (16.45 g, 70.8 mmol), treated all at once with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO, CAS No.2564-83-2, 1.084 g, 6.94 mmol), stirred at -5° C. for 5 minutes, allowed to warm to room temperature and stirred for 20 minutes. Mixture was diluted with CH2Cl2 (100 mL) and filtered through diatomaceous earth to remove solids. The CH2Cl2 layer was washed with saturated Na2CO3 (180 mL), washed with 1 N HCl (180 mL), washed with brine (180 mL), washed with saturated ammonium chloride (3*180 mL), dried (MgSO4), filtered, and concentrated on the rotory evaporator without heating to provide the title compound (8.77 g, 68.4 mmol, 99% yield). 1H NMR (501 MHz, CDCL3) δ 10.37 (s, 1H), 3.81 (s, 3H), 1.69-1.58 (m, 4H).
76% Stage #1: methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -78 - -45℃; for 0.5h; Stage #2: With N-ethyl-N,N-diisopropylamine In dichloromethane at -45 - 0℃; for 0.25h; 31.8 Step 8:
methyl 1-formylcyclopropanecarboxylate
Dimethyl sulfoxide (0.57 mL, 8.0 mmol) in methylene chloride (0.8 mL) was added to a solution of oxalyl chloride (0.34 mL, 4.0 mmol) in methylene chloride (5 mL) at -78° C. over 10 min. The resulting mixture was warmed to -60° C. over 25 min then a solution of methyl 1-(hydroxymethyl)cyclopropanecarboxylate (0.40 g, 3.1 mmol) in methylene chloride (5 mL) was slowly added. The mixture was warmed to -45° C. over 30 mins then N,N-diisopropylethylamine (2.8 mL, 16 mmol) was added and the mixture was warmed to 0° C. over 15 min. The reaction mixture was poured into a cold 1 N HCl aqueous solution and extracted with diethyl ether. The combined extracts were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on a silica gel column eluting with EtOAc in hexane (0-20%) to give the desired product (0.30 g, 76%).
With trichloroisocyanuric acid In dichloromethane at -5 - 20℃; for 0.666667h; 22 Preparation 22Methyl 1 -form lcyclopropanecarboxylateMethyl l-(hydroxymethyl)cyclopropanecarboxylate (16.0 g, 123.07 mmol) is dissolved in dichloromethane (320 mL) and the mixture is cooled to -5 °C.Trichloroisocyanuric acid (29.1 g, 125.5 mmol) is added portionwise followed by the addition of TEMPO (1.9 g, 12.3 mmol). The reaction mixture is stirred at -5 °C for 20 min, allowed to warm to RT, and stirred for 20 min. The mixture is filtered through a pad of CELITE and diluted with dichloromethane (500 mL). The solution is washed with saturated Na2C03 (300 mL), 1 N HC1 (300 mL), brine (300 mL), and saturated ammonium chloride (3 x 200 mL). The organic portion is dried overMgS04, filtered, and concentrated under reduced pressure to obtain 19 g of the title compound, still containing dichloromethane (theoretical 15.75 g). The material is used as is in the next reaction. ¾ NMR(400 MHz, CDC13); δ 1.7-1.6 (m, 4H), 3.81 (s, 3H), 10.38 (s, 1H).
With Dess-Martin periodane In dichloromethane at 20℃; 13.2 Step 2: To a solution of methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate (3.11 g, 23.9 mmol) in DCM (80 mL) was added Dess-Martin periodinane (15.6 g, 36.8 mmol) and the mixture was stirred at it overnight. The reaction was quenched with a solution ofNa2S2O3 (17.5 g) and saturated aqueous NaHCO3 (80 mL). The organic layer was separated and the aqueous layer was further extracted with DCM. The combined organic layers were washed with saturated aq. NaHCO3, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford methyl 1-formylcyclopropane-1-carboxylate as yellow oil (3.20 g, cmde 100%).

  • 25
  • [ 88157-42-0 ]
  • [ 1383001-34-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran; toluene / 4 h / 0 - 70 °C 2: potassium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere
  • 26
  • [ 88157-42-0 ]
  • [ 1383001-35-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran; toluene / 4 h / 0 - 70 °C 2: potassium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere 3: sodium carbonate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / water; N,N-dimethyl-formamide / 2 h / 65 °C / Inert atmosphere
  • 27
  • [ 88157-42-0 ]
  • [ 1383001-36-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran; toluene / 4 h / 0 - 70 °C 2: potassium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere 3: sodium carbonate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / water; N,N-dimethyl-formamide / 2 h / 65 °C / Inert atmosphere 4: water; sodium hydroxide / tetrahydrofuran; methanol / 4 h / 50 °C
  • 28
  • [ 88157-42-0 ]
  • [ 1383001-37-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran; toluene / 4 h / 0 - 70 °C 2: potassium acetate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 3 h / 100 °C / Inert atmosphere 3: sodium carbonate / dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / water; N,N-dimethyl-formamide / 2 h / 65 °C / Inert atmosphere 4: water; sodium hydroxide / tetrahydrofuran; methanol / 4 h / 50 °C 5: water; trifluoroacetic acid / 5 h / 20 °C
  • 29
  • [ 88157-42-0 ]
  • [ 164513-38-6 ]
  • [ 1383001-33-9 ]
YieldReaction ConditionsOperation in experiment
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 0 - 70℃; for 4h; Example 100[0357] [Formula 129][0358] 1) In tetrahydrofuran (26 mL) was dissolved <strong>[164513-38-6]5-bromo-4-methylpyridin-2-ol</strong> (1.3 g), methyl l-(hydroxymethyl)cyclopropanecarboxylate (1.08 g) and triphenylphosphine (2.72 g), and 40% diethyl azodicarboxylate-toluene solution (4.72 mL) was added dropwise to the solution at 0C. The mixture was stirred at 70C for 4 hours. The reaction mixture was cooled to room temperature, water and ethyl acetate were added to the mixture, and the organic layer was washed with a saturated brine and dried over anhydrous sodium sulfate. After concentrating the mixture under reduced pressure, the obtained residue was purified by silica gel column chromatography (n-hexane: ethyl acetate=99: l to 99:5) to obtain methyl l-[(5-bromo-4-methylpyridin-2-yl)oxy]- methyljcyclopropanecarboxylate (2.08 g).MS (m/z): 300/302 [M+H]+
  • 30
  • [ 67-56-1 ]
  • [ 49640-66-6 ]
  • [ 88157-42-0 ]
YieldReaction ConditionsOperation in experiment
1.14 g With hydrogenchloride at 70℃; for 18h; 22-1.2 (2) A solution of Compound 2 (1.57 g) in tetrahydrofuran (15 mL) was ice-cooled under a nitrogen stream, anda 1M solution of a borane/tetrahydrofuran complex in tetrahydrofuran (12 mL) was added dropwise. After dropwiseaddition, the reaction solution was stirred at room temperature for 1.5 hours. The reaction solution was ice-cooled, andmethanol was added. After the mixture was concentrated under reduced pressure, the residue was dissolved in methanol(15 mL), 20% hydrochloric acid/methanol (4 mL) was added, and the mixture was stirred at 70 °C for 18 hours. Thereaction solution was concentrated under reduced pressure, to the residue was added an aqueous saturated sodiumbicarbonate solution, and the mixture was extracted with chloroform. The extract was washed with saturated brine, anddried over anhydrous magnesium sulfate. To this was added NH silica gel, and the mixture was stood. The mixture wasfiltered and concentrated under reduced pressure to obtain Compound 3 (1.14 g) as a colorless oil.MS (m/z): 131 [M+H]+
  • 31
  • [ 88157-42-0 ]
  • methyl 1-[(4-(4-fluorobenzyl)-4-[[(1R,2S)-2-phenylcyclopropyl](trifluoroacetyl)amino]methyl}piperidin-1-yl)methyl]cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: dimethyl sulfoxide; oxalyl dichloride / dichloromethane / 0.5 h / -78 - -45 °C 1.2: 0.25 h / -45 - 0 °C 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.08 h 2.2: 1 h / 20 °C 2.3: 4 h / 20 °C
  • 32
  • [ 88157-42-0 ]
  • methyl 1-[(4-(methoxymethyl)-4-[[(1R,2S)-2-phenylcyclopropyl](trifluoroacetyl)amino]-methyl}piperidin-1-yl)methyl]cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: dimethyl sulfoxide; oxalyl dichloride / dichloromethane / 0.5 h / -78 - -45 °C 1.2: 0.25 h / -45 - 0 °C 2.1: acetic acid / dichloromethane / 2 h / 20 °C 2.2: 2 h / 20 °C
  • 33
  • [ 88157-42-0 ]
  • 1-[4-(4-fluorobenzyl)-4-([(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclopropanecarboxylic acid trifluoroacetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: dimethyl sulfoxide; oxalyl dichloride / dichloromethane / 0.5 h / -78 - -45 °C 1.2: 0.25 h / -45 - 0 °C 2.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.08 h 2.2: 1 h / 20 °C 2.3: 4 h / 20 °C 3.1: sodium hydroxide; water / tetrahydrofuran; methanol / 40 °C 3.2: pH 2
  • 34
  • [ 88157-42-0 ]
  • 1-[4-(methoxymethyl)-4-([(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclopropanecarboxylic acid trifluoroacetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: dimethyl sulfoxide; oxalyl dichloride / dichloromethane / 0.5 h / -78 - -45 °C 1.2: 0.25 h / -45 - 0 °C 2.1: acetic acid / dichloromethane / 2 h / 20 °C 2.2: 2 h / 20 °C 3.1: sodium hydroxide; water / tetrahydrofuran; methanol / 40 °C 3.2: pH 2
  • 35
  • [ 88157-42-0 ]
  • 1-[4-methyl-4-([(1R,2S)-2-phenylcyclopropyl]amino}methyl)piperidin-1-yl]methyl}cyclopropanecarboxylic acid trifluoroacetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: dimethyl sulfoxide; oxalyl dichloride / dichloromethane / 0.5 h / -78 - -45 °C 1.2: 0.25 h / -45 - 0 °C 2.1: acetic acid / dichloromethane / 2 h / 20 °C 2.2: 2 h / 20 °C 3.1: sodium hydroxide; water / tetrahydrofuran; methanol / 40 °C 3.2: pH 2
  • 36
  • [ 88157-42-0 ]
  • C23H29F3N2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: dimethyl sulfoxide; oxalyl dichloride / dichloromethane / 0.5 h / -78 - -45 °C 1.2: 0.25 h / -45 - 0 °C 2.1: acetic acid / dichloromethane / 2 h / 20 °C 2.2: 2 h / 20 °C
  • 37
  • C11H18O5 [ No CAS ]
  • [ 88157-42-0 ]
YieldReaction ConditionsOperation in experiment
0.46 g With sodium tetrahydroborate In water at 0℃; for 0.5h; 31.7 Step 7:
methyl 1-(hydroxymethyl)cyclopropanecarboxylate
Isobutyl chloroformate (0.61 mL, 4.7 mmol) was added to a solution of 1-(methoxycarbonyl)cyclopropanecarboxylic acid (Alfa Aesar, catNo.H25828: 0.57 g, 3.9 mmol) and triethylamine (1.1 mL, 7.8 mmol) in tetrahydrofuran (10 mL) at 0 OC. The resulting mixture was stirred at 0° C. for 30 min then filtered and washed with THF (2 mL). The filtrate was cooled to 0° C. and then a solution of sodium tetrahydroborate (0.30 g, 7.9 mmol) in water (2 mL) was added. The reaction mixture was stirred for 30 min then diluted with ethyl acetate, washed with saturated NaHCO3 aqueous solution, water and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The residue (0.46 g) was used in the next step without further purification.
  • 38
  • [ 88157-42-0 ]
  • methyl 1-(difluoromethyl)cyclopropane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: Dess-Martin periodane / dichloromethane / 20 °C 2: diethylamino-sulfur trifluoride / dichloromethane / 20 °C
  • 39
  • [ 88157-42-0 ]
  • [ 1267856-63-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: Dess-Martin periodane / dichloromethane / 20 °C 2: diethylamino-sulfur trifluoride / dichloromethane / 20 °C 3: lithium diisopropyl amide / tetrahydrofuran; ethylbenzene; n-heptane / -78 - 20 °C / Inert atmosphere
  • 40
  • [ 88157-42-0 ]
  • 5-(1-(difluoromethyl)cyclopropyl)isoxazol-3-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: Dess-Martin periodane / dichloromethane / 20 °C 2: diethylamino-sulfur trifluoride / dichloromethane / 20 °C 3: lithium diisopropyl amide / tetrahydrofuran; ethylbenzene; n-heptane / -78 - 20 °C / Inert atmosphere 4: hydroxylamine sulfate; sodium hydrogencarbonate / water; methanol / 85 °C
  • 41
  • [ 88157-42-0 ]
  • N-(5-(1-(difluoromethyl)cyclopropyl)isoxazol-3-yl)-2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: Dess-Martin periodane / dichloromethane / 20 °C 2: diethylamino-sulfur trifluoride / dichloromethane / 20 °C 3: lithium diisopropyl amide / tetrahydrofuran; ethylbenzene; n-heptane / -78 - 20 °C / Inert atmosphere 4: hydroxylamine sulfate; sodium hydrogencarbonate / water; methanol / 85 °C 5: pyridine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / ethyl acetate / 60 °C
  • 42
  • [ 88157-42-0 ]
  • methyl 1-[4-oxo-7-(trifluoromethoxy)-3,4-dihydro-2H-1-benzopyran-2-yl]cyclopropane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid / dichloromethane / 0.42 h / -5 - 20 °C / Inert atmosphere 2: acetic acid; pyrrolidine / toluene / 70 °C
  • 43
  • [ 100-39-0 ]
  • [ 88157-42-0 ]
  • C13H16O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.333333h; Cooling with ice; Stage #2: benzyl bromide In tetrahydrofuran; mineral oil at 0 - 20℃;
Stage #1: methyl 1-(hydroxymethyl)cyclopropane-1-carboxylate With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.333333h; Cooling with ice; Stage #2: benzyl bromide In tetrahydrofuran; mineral oil at 0 - 20℃; To a stirred suspension of 60% sodium hydride (NaH) in mineral oil (0.120 g, 30.0 mmol) in anhydrous THF (10 mL), cooled in an ice bath, was added methyl 1-hydroxymethyl cyclopropanecarboxylic acid (10.0 mmol, 1.30 g). The resultant suspension was stirred for 20 mm at room temperature. Benzyl bromide (10.0 mmol, 1.71 g, 1.21 ml) was slowly added at 0 °C, and the reaction was stirred at room temperature overnight. The reaction suspension was chilled in an ice bath, and the excess NaH was quenched with water (15 mL). The reaction mixture was extracted with ethyl acetate (3x25 mL). The combined organics were dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, 10 % ethyl acetate in hexanes) to deliver S10.
  • 44
  • [ 88157-42-0 ]
  • [ 1346641-23-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.33 h / 20 °C / Cooling with ice 1.2: 0 - 20 °C 2.1: lithium hydroxide monohydrate / tetrahydrofuran; water; methanol
  • 45
  • [ 88157-42-0 ]
  • 1-((1,3-dioxoisoindolin-2-yl)methyl)cyclopropane-1-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran / 12 h / 0 - 20 °C 2.1: sodium hydroxide / 1,4-dioxane; water / 3 h / 0 - 20 °C 2.2: 1 h / 150 °C
  • 46
  • [ 88157-42-0 ]
  • (1R,2R)-1-((benzyloxy)methyl)-2-(4-(methoxycarbonyl)phenyl)cyclopropane-1-carboxyli c acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.33 h / 20 °C / Cooling with ice 1.2: 0 - 20 °C 2.1: lithium hydroxide monohydrate / tetrahydrofuran; water; methanol 3.1: palladium diacetate; sodium carbonate; silver carbonate; (S)-N-(1-(dimethylamino)-3-phenylpropan-2-yl)acetamide / 16 h / 80 °C / Sealed tube
  • 47
  • [ 88157-42-0 ]
  • (1R,2R)-1-((1,3-dioxoisoindolin-2-yl)methyl)-2-(4-(methoxycarbonyl)phenyl) cyclopropane-1-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran / 12 h / 0 - 20 °C 2.1: sodium hydroxide / 1,4-dioxane; water / 3 h / 0 - 20 °C 2.2: 1 h / 150 °C 3.1: palladium diacetate; sodium carbonate; silver carbonate; (S)-N-(1-(dimethylamino)-3-phenylpropan-2-yl)acetamide / 16 h / 80 °C / Sealed tube
  • 48
  • [ 85-41-6 ]
  • [ 88157-42-0 ]
  • C14H13NO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 20℃; for 12h;
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 20℃; for 12h; Diethyl azodicarboxylate (7.50 mmol) was added to a cooled (0°C) solution of methyl 1-hydroxymethyl cyclopropanecarboxylate (651 mg, 5.00 mmol), triphenylphosphine (1.97 g,7.50 mmcl) and phthalimide (1.103 g, 7.50 mmcl) in THF (12 mL). After being stirred at room temperature for 12 h, the reaction mixture was concentrated under vacuum and purified by column chromatography on silica gel (eluent: EtOAc/hexanes = 1: 5) to give S11.
  • 49
  • [ 88157-42-0 ]
  • C14H14N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 3 h / 30 °C / Cooling with ice 2: caesium carbonate / N,N-dimethyl-formamide / 100 °C
  • 50
  • [ 88157-42-0 ]
  • C13H12N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 3 h / 30 °C / Cooling with ice 2: caesium carbonate / N,N-dimethyl-formamide / 100 °C 3: lithium hydroxide monohydrate / tetrahydrofuran; water / 15 - 30 °C
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