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[ CAS No. 1570-95-2 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 1570-95-2
Chemical Structure| 1570-95-2
Chemical Structure| 1570-95-2
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Product Details of [ 1570-95-2 ]

CAS No. :1570-95-2 MDL No. :MFCD00236056
Formula : C9H12O2 Boiling Point : -
Linear Structure Formula :- InChI Key :BPBDZXFJDMJLIB-UHFFFAOYSA-N
M.W : 152.19 Pubchem ID :254178
Synonyms :

Calculated chemistry of [ 1570-95-2 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.33
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 2.0
Molar Refractivity : 43.35
TPSA : 40.46 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.8 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.78
Log Po/w (XLOGP3) : 0.61
Log Po/w (WLOGP) : 0.75
Log Po/w (MLOGP) : 1.26
Log Po/w (SILICOS-IT) : 1.55
Consensus Log Po/w : 1.19

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.37
Solubility : 6.44 mg/ml ; 0.0423 mol/l
Class : Very soluble
Log S (Ali) : -1.03
Solubility : 14.1 mg/ml ; 0.0925 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.09
Solubility : 1.24 mg/ml ; 0.00817 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 1570-95-2 ]

Signal Word:Danger Class:N/A
Precautionary Statements:P280-P305+P351+P338+P310 UN#:N/A
Hazard Statements:H318 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1570-95-2 ]

* 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 [ 1570-95-2 ]

[ 1570-95-2 ] Synthesis Path-Downstream   1~93

  • 1
  • [ 1570-95-2 ]
  • [ 40893-99-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogen bromide; acetic acid Erwaermen des Reaktionsprodukts mit Aethanol und wenig wss. HBr;
With N-Bromosuccinimide; triphenylphosphine In dichloromethane 1.) ice cooling, 0.5 h, 2.) RT, 1 h;
With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0 - 20℃; for 0.5h; 4.2. General procedure 1: preparation of 1,3-dibromides from 1,3-diols General procedure: N-Bromosuccinimide (2.2 mmol) was added at 0 °C to a mixture of diol (1.0 mmol) and triphenylphosphine (2.2 mmol) in dichloromethane (10.0 mL). The cooling bath was removed and the reaction mixture was stirred at room temperature for 30 min. The solvent was evaporated and the product was purified by column chromatography (Silicagel, 40-63 μm, pentane).
With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0℃; for 7h; Typical Procedure for TBS-Protected Methyl Halide Alcohols: General procedure: To a mixture of diol (1 equivalent) in dichloromethane (0.1 M), N-bromosuccinimide (1 equivalent) and triphenylphosphine (1 equivalent) was added at 0°C. The reaction stirred for 7 hours after which the reaction was concentrated. The crude mixture was purified by silica gel column chromatography (30% ethyl acetate/hexanes) to obtain colorless oil as the monobrominated alcohol. The alcohol was used in the next reaction. To a mixture of unprotected alcohol (1 equivalent) in THF (0.2 M), TBSCl (2 eqvuivalents) and imidazole were added (3 equivalents). The reaction stirred overnight and then quenched with water and extracted with ethyl acetate. The organic layers were dried over filtered and concentrated in vacuo. The crude mixture was purified by silica gel chromatography (20% ethyl acetate/hexanes) to yield the desired product.(3-Bromo-2-phenylpropoxy)(tert-butyl)dimethylsilane (2a): colorless oil (2.6 g, 62% yield): 1H NMR (400 MHz, CDCl3): δ 7.28 (m, 5 H), 3.77-3.95 (m, 3 H), 3.62 (m, 1 H), 3.12 (m, 1 H), 0.87 (s, 9 H), 0.01 (s, 3 H), -0.01 (s, 3 H) ppm; 13C NMR (126 MHz, CDCl3) 140.5, 128.5, 128.1, 127.3, 65.1, 50.2, 34.9, 25.9, 18.4, -5.4 ppm; HRMS (C15H25BrOSi, ESI): calcd. 329.0931, [M+H]+ found 329.0945.
With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0℃; for 7h; Typical Procedure for TBS-Protected Methyl Halide Alcohols: General procedure: To a mixture of diol (1 equivalent) in dichloromethane (0.1 M), N-bromosuccinimide (1 equivalent) and triphenylphosphine (1 equivalent) was added at 0°C. The reaction stirred for 7 hours after which the reaction was concentrated. The crude mixture was purified by silica gel column chromatography (30% ethyl acetate/hexanes) to obtain colorless oil as the monobrominated alcohol. The alcohol was used in the next reaction. To a mixture of unprotected alcohol (1 equivalent) in THF (0.2 M), TBSCl (2 eqvuivalents) and imidazole were added (3 equivalents). The reaction stirred overnight and then quenched with water and extracted with ethyl acetate. The organic layers were dried over filtered and concentrated in vacuo. The crude mixture was purified by silica gel chromatography (20% ethyl acetate/hexanes) to yield the desired product.(3-Bromo-2-phenylpropoxy)(tert-butyl)dimethylsilane (2a): colorless oil (2.6 g, 62% yield): 1H NMR (400 MHz, CDCl3): δ 7.28 (m, 5 H), 3.77-3.95 (m, 3 H), 3.62 (m, 1 H), 3.12 (m, 1 H), 0.87 (s, 9 H), 0.01 (s, 3 H), -0.01 (s, 3 H) ppm; 13C NMR (126 MHz, CDCl3) 140.5, 128.5, 128.1, 127.3, 65.1, 50.2, 34.9, 25.9, 18.4, -5.4 ppm; HRMS (C15H25BrOSi, ESI): calcd. 329.0931, [M+H]+ found 329.0945.

  • 2
  • [ 1570-95-2 ]
  • [ 85291-68-5 ]
YieldReaction ConditionsOperation in experiment
81% With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0 - 20℃; for 4.5h; Inert atmosphere;
79% With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0 - 20℃; for 2h; Schlenk technique;
66% With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0 - 20℃; for 0.5h; 4.2. General procedure 1: preparation of 1,3-dibromides from 1,3-diols General procedure: N-Bromosuccinimide (2.2 mmol) was added at 0 °C to a mixture of diol (1.0 mmol) and triphenylphosphine (2.2 mmol) in dichloromethane (10.0 mL). The cooling bath was removed and the reaction mixture was stirred at room temperature for 30 min. The solvent was evaporated and the product was purified by column chromatography (Silicagel, 40-63 μm, pentane).
With pyridine; phosphorus tribromide

  • 3
  • [ 83-13-6 ]
  • [ 60-12-8 ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
10% With sodium tetrahydroborate; sodium dihydrogenphosphate IV The use of sodium borohydride in the preparation of 2-Phenyl 1,3 Propandiol leads to the development of basic pH conditions during the reaction. These pH conditions promote the formation of 2-phenyl ethanol which leads to low purity and low yield of the 2-phenyl-l ,3- propanediol product.[0036] The formation of 2-phenyl ethanol during the reaction between diethyl phenylmalonate and sodium borohydride was determined in the presence or absence of sodium dihydrogen phosphate as a buffer. As demonstrated in Table 1 , the addition of the buffer to the reaction significantly reduced the formation of 2-phenyl ethanol and led to the formation of highly purified 2-phenyl- 1,3 -propanediol. The purity of 2-phenyl -1,3 -propanediol obtained in the presence of the buffer is significantly higher than the purity obtained using the standard reaction (91.6% purity versus 60% purity, respectively). Furthermore, the percentage of the 2- phenyl ethanol impurity which was produced in the presence of buffer was greatly reduced (4.7% of 2-phenyl ethanol when buffer was added to the reaction versus 10% of 2-phenyl ethanol in the absence of buffer). The percentage of other non-identified impurities (Impurity A and Impurity B) was also greatly reduced when the buffer was added to the reaction (for example, 0.14% of impurity A when the buffer was added to the reaction versus 1.8% of impurity A in the absence of buffer). The 2-phenyl- 1,3 -propanediol preparation process of the invention comprises further purification steps after which the percentage of total impurities is not more than about 1% .Table 1: The effect of buffer addition on impurity formation during the reaction
With ethanol; copper oxide-chromium oxide at 150℃; Hydrogenation;
  • 4
  • [ 83-13-6 ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
99.6% 1) Under argon protection,diethyl 2-phenyl-malonate, mix the reducing agent and tetrahydrofuran, controlling the reaction temperature to rise to 145 C, the pressure rises to 3 atmospheres,add 4 mol/L sodium hydroxide solution dropwise,the dropping time for controlling the aqueous sodium hydroxide solution is 50 minutes.When the sodium hydroxide aqueous solution is added for 6 minutes,Start adding a 25% tetrabutylammonium chloride aqueous solution.The dropping time of the aqueous solution of tetrabutylammonium chloride was controlled to be 11 min. After the addition of the aqueous sodium hydroxide solution, toluene was added to control the addition time of toluene to 8 min, and then the reaction temperature was controlled to 156 C, and the reaction pressure was 5 atmospheres. The reaction was continued for 3 hours and the cooling was completed.The preparation method of the reducing agent: will be 350 purpose zinc powder, 350 purpose aluminum powder and 150 activated carbon even grinding the purpose, in the mass fraction of 0.5% acetic acid solution 16 min after filtering, the resulting solid is washed, in the argon replacement air in the drying box for after 85 C and dried to obtain the; zinc powder, aluminum powder and the activated carbon of the consumption ratio of 1 muM: 0.9 muM: 160 g.2-phenylmalonic acid diethyl ester and the mass ratio of the reducing agent of 1: 2.35; 2 - phenyl - c diethyl malonate with tetrahydrofuran, toluene and the ratio of the amount of 1 g: 5 ml: 4 ml; 2 - phenylmalonic acid diethyl ester with sodium hydroxide aqueous solution consumption ratio of 1 muM: 1100 ml; 2 - phenylmalonic acid diethyl ester and tetrabutyl ammonium chloride aqueous solution consumption ratio of 1 muM: 200 ml.2) A system is cooled after filtering, layered, after washing the organic layer, after drying with anhydrous sodium sulfate, the rotavapor for concentrated evaporate the solvent to obtain the product. The molar yield of 99.6%, GC purity 99.3%.
69% With sodium tetrahydroborate; sodium dihydrogen phosphate monohydrate; ethanol; at 15℃;Product distribution / selectivity; A mixture of 20g of diethyl phenylmalonate, 6.6g of sodium dihydrogen phosphate monohydrate and 140 ml of absolute ethanol was cooled to 15C after which 7.1g of solid sodium borohydride was added. The reaction was completed by quenching the excess of sodium borohydride with 10% HC1 solution and distilling the residual ethanol. 8 ml of NaOH 50% were added in order to obtain a pH of between about 8.0 to about 9.0. The obtained 2- phenyl- 1 ,3 -propanediol was then extracted into 400 ml of ethyl acetate. The organic layer was washed with 40 ml of water and filtered through alumina. The precipitate was crystallized from toluene following solvent removal, to obtain 8.9g of 2-phenyl-l ,3-propanediol with a yield of 69%
28% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; Under an Ar atmosphere, diethyl phenylmalonate (4.5 g, 19.0 mmol) was added dropwise to a solution of LiAlH4 (1.9 g, 50.0 mmol) in THF (90 mL) at 0C. The reaction mixture was warmed up to room temperature and stirred overnight. After the addition of Na2SO4, the mixture was extracted with AcOEt (30mL×3) and the combined organic layer was washed with H2O (50mL×2) and brine (50mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (eluent: hexane/AcOEt=1:3) to give 2-phenyl-1,3-propanediol (0.85 g, 28%) as colorless oil. Under an Ar atmosphere, a solution of p-toluenesulfonyl chloride (6.0 g, 31.5 mmol) in MeCN (16mL) was added dropwise to a solution of 2-phenyl-1,3-propanediol (1.6g, 10.5mmol), Me3N·HCl (0.20g, 2.1mmol), and Et3N (3.2g, 31.5mmol) in MeCN (7mL) at 0C and stirred for 5h at the same temperature. After the addition of N,N?-dimethylethylenediamine (2mL), the mixture was extracted with AcOEt (30mL×3) and the combined organic layer was washed with H2O (50mL×2) and brine (50mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (eluent: hexane/AcOEt=3:1) to give 2-phenyl-1,3-propaneditosylate (0.88g, 18%) as a colorless solid. Under an Ar atmosphere, thiourea (1.4g, 19.0mmol) was added to a solution of 2-phenyl-1,3-propaneditosylate (0.88g, 1.9mmol) in EtOH (10mL) at room temperature, and the mixture was heated under reflux overnight. After the reaction mixture was cooled down to room temperature, 20% NaOH (10mL) was added and the whole mixture was heated under reflux overnight. After the addition of 1M HCl (30mL), the mixture was extracted with CH2Cl2 (50mL×3) and the combined organic layer was washed with H2O (50mL×1) and brine (50mL×1). The organic layer was dried over MgSO4 and concentrated in vacuo to give 2-phenyl-1,3-propanedithiol (0.48g) as yellowish oil, which was used to the next reaction without further purification. According to the Method A, 1aa was prepared from the above-obtained 2-phenyl-1,3-propanedithiol and p-anisaldehyde (0.27 g, 75% over two steps). Recrystallized from AcOEt, colorless needles, mp 165-167C. IR (neat): 2892, 1605, 1509, 1248, 1170, 1022, 851, 818, 767, 725cm-1. 1H NMR (400MHz, CDCl3/TMS) delta (ppm): 2.92-2.96 (m, 2H), 3.16-3.30 (m, 3H), 3.80 (s, 3H), 5.22 (s, 1H), 6.88 (d, J=8.8Hz, 2H), 7.22-7.27 (m, 3H), 7.32-7.36 (m, 2H), 7.44 (d, J=8.8Hz, 2H). 13C{1H} NMR (100MHz, CDCl3) delta (ppm): 38.3, 42.8, 50.4, 44.3, 114.2, 126.7, 127.1, 128.87, 128.92, 130.3, 144.9, 159.7. LRMS (EI) m/z: 302 (M+). HRMS: calcd for C17H18OS2: 302.0799, found: 302.0780.
  • 5
  • [ 1570-95-2 ]
  • [ 6781-42-6 ]
  • [ 133401-81-7 ]
YieldReaction ConditionsOperation in experiment
41.9% With toluene-4-sulfonic acid In benzene for 16h; Heating;
  • 6
  • [ 1570-95-2 ]
  • [ 13482-22-9 ]
  • [ 76626-12-5 ]
YieldReaction ConditionsOperation in experiment
54% With toluene-4-sulfonic acid In benzene for 4.6h; Heating;
  • 7
  • [ 1570-95-2 ]
  • [ 133401-80-6 ]
  • [ 133401-79-3 ]
YieldReaction ConditionsOperation in experiment
40% With 3 A molecular sieve; toluene-4-sulfonic acid In benzene for 10h; Heating;
  • 8
  • [ 1570-95-2 ]
  • [ 10317-13-2 ]
YieldReaction ConditionsOperation in experiment
58% Stage #1: 2-phenylpropane-1, 3-diol With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.25h; Inert atmosphere; Stage #2: With p-toluenesulfonyl chloride In tetrahydrofuran; hexane at 0℃; for 1h; Inert atmosphere; Stage #3: With n-butyllithium In tetrahydrofuran; hexane at 50℃; Inert atmosphere;
Yield given. Multistep reaction;
Stage #1: 2-phenylpropane-1, 3-diol With n-butyllithium; p-toluenesulfonyl chloride Stage #2: With n-butyllithium In tetrahydrofuran at 0 - 60℃;
With n-butyllithium In tetrahydrofuran
Stage #1: 2-phenylpropane-1, 3-diol With n-butyllithium In tetrahydrofuran Inert atmosphere; Stage #2: With p-toluenesulfonyl chloride In tetrahydrofuran Inert atmosphere; Stage #3: With n-butyllithium In tetrahydrofuran Inert atmosphere;

  • 10
  • [ 2613-89-0 ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
91% With borane In tetrahydrofuran at -30℃; for 144h;
85% With borane In tetrahydrofuran at 0℃; other malonic acids; var. temperatures;
54% With indium(III) bromide; 1,1,3,3-Tetramethyldisiloxane In toluene at 60℃; for 15h; Inert atmosphere;
With borane-THF In tetrahydrofuran at 0℃; other phenyl carboxylic acids; var. temp.;
In tetrahydrofuran 33 (R,S)-[(2-Phenyl-3-trimethylsilyloxy)propyl]triphenylphosphonium iodide EXAMPLE 33 (R,S)-[(2-Phenyl-3-trimethylsilyloxy)propyl]triphenylphosphonium iodide To 5.11 g of phenylmalonic acid in 50 mL of ether cooled to 0° C. was added 60 mL of a 1M solution of lithium aluminum hydride in THF. After stirring the mixture at room temperature overnight, the excess lithium aluminum hydride was quenched with ethyl acetate and dilute hydrochloric acid. The 1,3-dihydroxy-2-phenylpropane was isolated by ether extraction, and subsequent purification by flash chromatography gave 1.34 g of product characterized by NMR.

  • 12
  • [ 1570-95-2 ]
  • [ 75-36-5 ]
  • [ 98017-92-6 ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine at 0℃;
  • 13
  • [ 83-13-6 ]
  • [ 60-12-8 ]
  • [ 1570-95-2 ]
  • [ 101-97-3 ]
YieldReaction ConditionsOperation in experiment
1: 10% 2: 12% 3: 45% With Na(PEG-400)2BH2 In tetrahydrofuran at 80℃; for 4h;
1: 45% 2: 12% 3: 15% With Na(PEG-400)2BH2 In tetrahydrofuran at 80℃; for 4h;
  • 14
  • [ 1570-95-2 ]
  • [ 18162-48-6 ]
  • [ 173423-55-7 ]
YieldReaction ConditionsOperation in experiment
62% With sodium hydride In tetrahydrofuran 1.) r.t., 1 h, 2.) r.t., 8 h;
59% With sodium hydride In tetrahydrofuran at 20℃; for 12h;
59% With sodium hydride In tetrahydrofuran at 20℃; for 12h; Cooling with ice; R05 Reaction R05 was performed by adding a solution of 2-phenylpropane-1,3-diol (5 g, 33 mmol) in THF (25 mL) dropwise to a stirred and ice cooled suspension of NaH (1.5 g, 36 mmol) in THF (15 mL). The ice bath was removed, and reaction was warmed up to room temperature for 12 h. The mixture was quenched with ice, diluted with EtOAc (300 mL) and washed with brine (2x 150 mL). The separated organic layer was dried with Na2S04, and concentrated under reduced pressure, purified by column chromatography (100% hexane) to afford 3-((tert-butyldimethylsilyl)oxy)-2-phenylpropan-1-ol as yellow solid in a yield of 5 g (59%; Rf = 0.8 in hexane : EtOAc = 100: 1, v/v). 1H NMR (400 MHz, CDCl3) d 7.33-7.30 (m, 2H), 7.24 (brs, 1H), 7.22-7.20 (m, 2H), 4.13-4.05 (m, 2H), 3.93- 3.87 (m, 2H), 3.12-3.05 (m, 1H), 1.26 (t, J= 7.2 Hz, 2H), 0.90 (s, 9H), 0.06 (s, 6H). The 1H NMR data agreed with the reported spectrum of this compound.
52% With dmap; triethylamine In dichloromethane for 12h; Ambient temperature;
46% With dmap; triethylamine In dichloromethane at 20℃; for 12h; 1 Step 1. Synthesis of 3-[(tert-butyldimethylsilyl)oxy]-2-phenylpropan-1-ol. Into a 100-mL round-bottom flask, 2-phenylpropane-1,3-diol (2.5 g, 16.43 mmol) was dissolved in dichloromethane (30 mL). Then tert-butyldimethylsilyl chloride (2.6 g, 17.25 mmol) and 4-dimethylaminopyridine (20 mg, 0.16 mmol) were added, followed by triethylamine (2.7 mL, 19.42 mmol). The mixture was stirred for 12 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was subjected to purification by FCC eluting with ethyl acetate/petroleum ether (1:5). This afforded the title compound (2 g, 46%) as a yellow oil. MS : (ES, m/z): 267 [M+H]+.
32% With dmap; triethylamine In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere; liii.a a) 3-((ie f-Butyldimethylsilyl)oxy)-2-phenylpropan-1 -ol I152 To a solution of 2-phenylpropane-1,3-diol (5.0 g, 32.9 mmol), TBDMSCI (4.95 g, 32.9 mmol) and DMAP (40 mg, 0.329 mmol) in DCM (60 mL) at 0 °C under N2 was added Et3N (3.66 g, 36.2 mmol) and the mixture was stirred at RT for 12 h. The mixture was partitioned between water and DCM, the layers were separated and the organic phase was dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (Pet. ether/EtOAc = 30/1) to give the title compound (2.75 g, 32%) as a colorless oil. LCMS-C: Rt2.69 min; m/z 267.1 [M+H]+.
With dmap; triethylamine In dichloromethane for 12h; Ambient temperature; Yield given;
972 mg Stage #1: 2-phenylpropane-1, 3-diol With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 0.333333h; Stage #2: tert-butyldimethylsilyl chloride In tetrahydrofuran; mineral oil at 0 - 20℃; for 16h; 2-5-1 3-(tert-Butylmethylsilyl)oxy-2-phenylpropylamine To a solution of 2-phenylpropane-1,3-diol (556 mg) in tetrahydrofuran (20 mL) was added sodium hydride (60% dispersion in oil, 153 mg) at 0°C, and the mixture was stirred at room temperature for 20 minutes. To the mixture was added tert-butyldimethylchlorosilane (578 mg) at 0°C, and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added a saturated aqueous solution of sodium bicarbonate, and the crude product was extracted with ethyl acetate. The extract was washed with brine, and dried over sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane) to afford 3-(tert-butyldimethylsilyloxy)-2-phenylpropan-1-ol (972 mg).
972 mg Stage #1: 2-phenylpropane-1, 3-diol With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 0.333333h; Stage #2: tert-butyldimethylsilyl chloride In tetrahydrofuran; mineral oil at 0 - 20℃; for 16h; 2-5-1 3- (tert-Butyldimethylsilyl) oxy-2-phenylpropylamine Sodium hydride (60% oil dispersion, 153 mg) was added at 0 ° to a solution of 2-phenylpropane-1,3-diol (556 mg) in tetrahydrofuran (20 mL) and stirred at room temperature for 20 minutes. To this mixture was added tert-butyldimethylchlorosilane (578 mg) at 0 ° C. and the mixture was stirred at room temperature for 16 hours. Saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the crude product was extracted with ethyl acetate. The extract was washed with saturated brine and then dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane)3- (tert-butyldimethylsilyloxy) -2-phenylpropan-1-ol (972 mg).To a solution of the product (972 mg) in tetrahydrofuran (20 mL) were added phthalimide (590 mg), triphenylphosphine (1.05 g), azodicarboxylic acid diethyl ester toluene(2.2 mol / L, 1.8 mL), and the mixture was stirred at room temperature for 16 hours. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane)N- {3 - [(tert-butyldimethylsilyl) oxy] -2-phenylpropyl} phthalimide (1.38 g).Hydrazine monohydrate (1.75 g) was added to a solution of the product (1.38 g) in ethanol (17 mL), and the mixture was stirred at 80 ° C. for 2 hours. Insolubles were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by aminopropyl silica gel column chromatography (eluent: ethyl acetate / n-hexane) to give the title compound (791 mg). Structural formula, spectral data and purification conditions are shown in Table 26

  • 15
  • [ 1570-95-2 ]
  • [ 637-88-7 ]
  • 3,12-Diphenyl-1,5,10,14-tetraoxa-dispiro[5.2.5.2]hexadecane [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With toluene-4-sulfonic acid In benzene Heating;
  • 16
  • [ 1570-95-2 ]
  • [ 530-62-1 ]
  • [ 25451-53-0 ]
YieldReaction ConditionsOperation in experiment
63% Stage #1: 2-phenylpropane-1, 3-diol; 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 1h; Stage #2: With ammonia In tetrahydrofuran at -48℃; for 3h;
  • 17
  • [ 1570-95-2 ]
  • [ 2746-25-0 ]
  • [ 443284-37-5 ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: 2-phenylpropane-1, 3-diol With sodium hydride In tetrahydrofuran at 0℃; for 1h; Stage #2: p-Methoxybenzyl bromide With tetra-(n-butyl)ammonium iodide In tetrahydrofuran at 20℃; for 2h;
  • 18
  • [ 466680-46-6 ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
89% With water; Selectfluor In acetonitrile at 20℃; for 5h;
  • 19
  • 2-(4-methoxy-phenyl)-5-phenyl-[1,3]dioxane [ No CAS ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
90% With water; Selectfluor In acetonitrile at 20℃; for 5h;
  • 20
  • C19H28O4 [ No CAS ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
94% With water; Selectfluor In acetonitrile at 20℃; for 5h;
  • 21
  • [ 110-87-2 ]
  • [ 1570-95-2 ]
  • C19H28O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With scandium tris(trifluoromethanesulfonate) In ethyl acetate at 20℃; for 1h;
  • 22
  • [ 24424-99-5 ]
  • [ 1570-95-2 ]
  • carbonic acid <i>tert</i>-butyl ester 3-hydroxy-2-phenyl-propyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With cerium(III) chloride In tetrahydrofuran
  • 23
  • [ 1570-95-2 ]
  • [ 93-97-0 ]
  • benzoic acid 3-hydroxy-2-phenyl-propyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With cerium(III) chloride In tetrahydrofuran
  • 24
  • [ 1570-95-2 ]
  • [ 98-88-4 ]
  • benzoic acid 3-hydroxy-2-phenyl-propyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With N-ethyl-N,N-diisopropylamine; O-diphenylphosphanyl-cinchonine In dichloromethane at 0℃; for 1.5h;
  • 25
  • [ 1570-95-2 ]
  • [ 66-77-3 ]
  • [ 475145-42-7 ]
YieldReaction ConditionsOperation in experiment
74% With toluene-4-sulfonic acid In toluene Heating;
  • 26
  • [ 110-87-2 ]
  • [ 1570-95-2 ]
  • [ 466680-46-6 ]
YieldReaction ConditionsOperation in experiment
49% With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 5.5h;
  • 27
  • [ 6296-95-3 ]
  • [ 1570-95-2 ]
  • [ 119-61-9 ]
  • [ 80001-45-2 ]
YieldReaction ConditionsOperation in experiment
1: 85% 2: 89% With PTAB; N-benzyl-N,N,N-triethylammonium chloride; antimony(III) bromide In dimethyl sulfoxide at 20℃; for 42h;
  • 28
  • [ 1570-95-2 ]
  • [ 579-43-1 ]
  • [ 80001-45-2 ]
YieldReaction ConditionsOperation in experiment
80% With PTAB; N-benzyl-N,N,N-triethylammonium chloride; antimony(III) bromide In dimethyl sulfoxide at 20℃; for 42h;
  • 29
  • [ 1570-95-2 ]
  • [ 1439-07-2 ]
  • [ 80001-45-2 ]
YieldReaction ConditionsOperation in experiment
79% With PTAB; N-benzyl-N,N,N-triethylammonium chloride; antimony(III) bromide In dimethyl sulfoxide at 20℃; for 46h;
  • 31
  • [ 1570-95-2 ]
  • N-[3-(acetylamino)-2-phenylpropyl]-2-methoxyacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C 4: Pseudomonas cepacia lipase C / dioxane / 117 h / 30 °C 5: 94 percent / Et3N / CH2Cl2 / 4 h / 20 °C
Multi-step reaction with 5 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C 4: Candida antarctica lipase type B / dioxane / 117 h / 30 °C 5: 94 percent / Et3N / CH2Cl2 / 4 h / 20 °C
Multi-step reaction with 5 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C 4: 28 percent / CH2Cl2 / 4 h / 20 °C 5: 94 percent / Et3N / CH2Cl2 / 4 h / 20 °C
  • 32
  • [ 1570-95-2 ]
  • allyl (3-amino-2-phenylpropyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C 4: 18 percent / CH2Cl2 / 4 h / 20 °C
  • 33
  • [ 1570-95-2 ]
  • [ 957131-07-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C 4: 73 percent / Pseudomonas cepacia lipase C I / benzene / 70 h / 30 °C
  • 34
  • [ 1570-95-2 ]
  • (R)-(-)-allyl [3-(acetylamino)-2-phenylpropyl]carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C 4: 73 percent / Pseudomonas cepacia lipase C I / benzene / 70 h / 30 °C 5: 94 percent / Et3N / CH2Cl2 / 4 h / 20 °C
  • 35
  • [ 1570-95-2 ]
  • [ 957131-05-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C 4: Pseudomonas cepacia lipase C / dioxane / 117 h / 30 °C
Multi-step reaction with 4 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C 4: Candida antarctica lipase type B / dioxane / 117 h / 30 °C
Multi-step reaction with 4 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C 4: 28 percent / CH2Cl2 / 4 h / 20 °C
  • 36
  • [ 1570-95-2 ]
  • [ 55165-09-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C
  • 37
  • [ 1570-95-2 ]
  • [ 873977-00-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 90 percent / pyridine / 24 h / 20 °C 2: sodium azide / dimethylformamide / 24 h / 55 °C 3: 210 mg / H2 / Pd/C / methanol / 24 h / 20 °C 4: Candida antarctica lipase type B / dioxane / 117 h / 30 °C
  • 38
  • [ 1570-95-2 ]
  • [ 110230-69-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: Py / 20 °C 2: 48 percent / porcine pancreatic lipase / aq. phosphate buffer / 1.2 h / 20 °C / pH 7
Multi-step reaction with 2 steps 1: 80 percent / NEt3 / 0 °C 2: Ambient temperature; porcine pancreas lipase (PPL), phosphate buffer pH 7 (kept constant with 1 N NaOH)
Multi-step reaction with 2 steps 1: H2SO4 2: H2O / porcine pancrease lipase pool on Eupergit C / 17 h / 4 °C / solvent: sodium phosphate buffer, pH=7
Multi-step reaction with 2 steps 1: triethylamine / 4-dimethylaminopyridine / CH2Cl2 / 1 h / Ambient temperature 2: 0.02M phosphate buffer, 1N NaOH / 4.5 h / Ambient temperature; PPL, pH 7

  • 39
  • [ 1570-95-2 ]
  • [ 110270-51-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 80 percent / NEt3 / 0 °C 2: Ambient temperature; porcine pancreas lipase (PPL), phosphate buffer pH 7 (kept constant with 1 N NaOH)
Multi-step reaction with 2 steps 1: H2SO4 2: H2O / porcine pancrease lipase pool on Eupergit C / 17 h / 4 °C / solvent: sodium phosphate buffer, pH=7
Multi-step reaction with 2 steps 1: triethylamine / 4-dimethylaminopyridine / CH2Cl2 / 1 h / Ambient temperature 2: 0.02M phosphate buffer, 1N NaOH / 4.5 h / Ambient temperature; PPL, pH 7
  • 40
  • [ 1570-95-2 ]
  • [ 17126-67-9 ]
  • 41
  • [ 1570-95-2 ]
  • [ 13580-37-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: TsOH / toluene / Heating 2: H2 / PtO2 / acetic acid / 2574.3 Torr / Ambient temperature
  • 42
  • [ 5894-79-1 ]
  • [ 108-10-1 ]
  • [ 2258-42-6 ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
70.05% With hydrogenchloride; sodium borohydrid; tetrabutyl-ammonium chloride; sodium carbonate In tert-butyl methyl ether; water 10 Preparation of 2-phenyl-1,3-propanediol EXAMPLE 10 Preparation of 2-phenyl-1,3-propanediol A one liter three-neck flask fitted with mechanical stirrer, thermometer, nitrogen inlet and addition funnel was charged with water (200 mL), tetrabutylammonium chloride (1.0 g) and 98% sodium borohydride (4.83 g, 0.125 mole). The solution was purged with nitrogen, then stirred and cooled to 4° C. in an ice bath. Crude methyl α-formylphenylacetate (90.6 g, 0.5 mole), prepared according to Example 9, was charged to the addition funnel, and rinsed in with t-butyl methyl ether (25 mL), and added to the above solution at 3°-8° C. The addition took a total of 100 minutes. After 20 minutes into the addition of formylacetate, a second charge of sodium borohydride (4.83 g) was added and rinsed in with water (20 mL). After an additional 1 hour and then again at 1.5 hours, sodium borohydride (4.83 g) in water (20 mL) was added to the batch. The slurry was held at 3° C. for an additional 6 hours, and then allowed to warm to room temperature overnight. The batch was cooled to 15° C., and concentrated hydrochloric acid (46 mL) was added. Methyl isobutyl ketone (MIBK, 100 mL) was added and the batch was stirred vigorously for 15 minutes. The pH of the batch was 1.0. Solid sodium carbonate (45 g) was added and the batch was stirred vigorously for 5 hours. The solids were separated by filtration and washed with MIBK. The solids were dried in vacuo at 65° C. (50.16 g). The aqueous layer from the main filtrate was extracted twice with the MIBK washes. The combined MIBK layers were washed with citric acid solution (10 mL, 5.6 g/15 mL water) and then with saturated sodium chloride solution (20 mL). The solution was filtered through Solka Floc and concentrated in vacuo to 75° C. The pale yellow oil (71.60 g) was crystallized from toluene (80 mL) to give 2-phenyl-1,3-propanediol (53.3 g, 70.05%) m.p. 52°-53.5° C.
  • 43
  • 2-methoxy-2-phenyl-1,3-propanediol [ No CAS ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
In ethanol; toluene 11 EXAMPLE 11 EXAMPLE 11 Into a 100 ml autoclave, 5 g (0.033 mole) of the 2-methoxy-2-phenyl-1,3-propanediol obtained in Example 7 and 50 ml of ethanol were charged, and 10 g of a 5% Pd/C catalyst was further added thereto, where the temperature was raised to 50° C. and the hydrogen pressure was set at 5 kg/cm2. In this state, the reaction was carried out for 6 hours. Thereafter the catalyst was removed and the ethanol was further evaporated to obtain 5.17 g of a crude product. The crude product thus obtained was dissolved in 15 g of toluene, and then cooled to precipitate crystals. Next, the crystals were collected by filtration, followed by drying to obtain 1.68 g (0.014 mole) of the desired product 2-phenyl-1,3-propanediol.
11 EXAMPLE 11 The yield of 2-phenyl-1,3-propanediol from 2-methoxy-2-phenyl-1,3-propanediol was 42%.
  • 44
  • [ 1570-95-2 ]
  • [ 530-62-1 ]
  • [ 211506-14-8 ]
  • Fluorofelbamate [ No CAS ]
  • [ 288302-42-1 ]
  • [ 25451-53-0 ]
  • [ 25451-15-4 ]
YieldReaction ConditionsOperation in experiment
78% Stage #1: 2-phenylpropane-1, 3-diol; 1,1'-carbonyldiimidazole; 2-fluoro-2-phenyl-1,3-propanediol In tetrahydrofuran Stage #2: With ammonium carbonate In tetrahydrofuran for 38 - 72h; Molecular sieve; 5 2-Fluoro-2-phenyl-1,3-propanediol dicarbamate (Fluorofelbamate) A flask was charged with 1.00 part of F-Diol and 9.50 parts of THF. The resulting solution was treated with 2.39 parts of 1,1'-carbonyldiiumidazole (CDI) in a single portion. After several hours a heavy precipitate formed which was stirred an additional 18-24 h. Next, 1.00 part of powdered activated molecular sieves (4 , 25μ) was added followed by 3.4 parts of ammonium carbonate. The slurry was stirred for 18-24 h, then treated with an additional 3.4 parts of ammonium carbonate. After an additional 18-24 h, the reaction mixture was allowed to settle for 2-24 h and the supernatant was removed. The remaining slurry was treated with ethyl acetate (5 parts), stirred, and filtered to remove solids. The filter cake was washed three times with 2.5 parts each of ethyl acetate. The organic phases were combined and concentrated to an oil, then dissolved in 5 parts ethyl acetate, and washed with 2.5 parts of water then 3 parts of 6 N hydrochloric acid. (An additional wash may be necessary if the pH of the aqueous acid wash is still basic by pH paper.) The ethyl acetate layer was then washed with 3 parts brine solution followed by 3 parts of sodium bicarbonate. The organic layer was dried over 1.0 part sodium sulfate, filtered, and concentrated in vacuo, while maintaining a bath temperature of 60-80° C., to a light-syrup (leaving approximately 1-2 parts ethyl acetate). This solution was then added to 5 parts of MTBE with stirring at which point crystallization commenced. The resulting white slurry was stirred 14-24 h and the solids were isolated by filtration and dried in vacuo at 60° C. The yield of crude 2-fluoro-2-phenyl-1,3-propanediol dicarbamate is typically 78-85% of theoretical. HPLC analysis indicated >98-99% (AUC) purity along with 0.5% 2-phenyl-1,3-propanediol and 0.3-0.5% 2-fluoro-2-phenyl-1,3-propanediol monocarbamate (“F-monocarbamate”). The crude product was further purified by dissolving 1.00 part fluorofelbamate in 10 parts of hot methanol-water (1:4). Cooling to ambient temperature and stirring overnight, followed by filtration, afforded the title compound as a white crystalline solid. Yields of crystallization processes are typically 93-97%. HPLC analysis indicated >99.5% AUC fluorofelbamate. Typically, less than 0.35% felbamate is present by HPLC. 1H-NMR (d6-DMSO, 500 MHz) 67 7.50-7.20 (m, 5 H, PhH), 6.8-6.2 (bd, 4 H, NH2), 4.42-4.20 (m, 4 H, CH2). Under the HPLC conditions described for Example 3, the retention times were: F-Diol (5.8 min), Diol (6.2 min), monocarbamate (8.8 min), F-monocarbamate (9.3 min), felbamate (12.3 min), fluorofelbamate (15.8 min).
  • 45
  • α-fluorophenylmalonate dipotassium salt [ No CAS ]
  • [ 1570-95-2 ]
  • [ 211506-14-8 ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: α-fluorophenylmalonate dipotassium salt With hydrogenchloride In tetrahydrofuran; 1,4-dioxane at 0 - 10℃; for 0.5h; Stage #2: With diborane In tetrahydrofuran; 1,4-dioxane at 2.5 - 20℃; for 18 - 24h; 4 A flask was charged with 1.00 part of F-K2PMA and 2.50 parts of THF. The thick slurry was externally cooled with ice and treated dropwise with a solution of 1.83 parts of 4 N HCl in dioxane so as to maintain the temperature between 2.5 and 10° C. After the addition was complete, the slurry was stirred for an additional 0.5 h and 14.59 parts of a 1 M solution of diborane in THF was added so as to maintain the temperature between 2.5° C. and 12° C. An initial exotherm was accompanied by evolution of gas. After the addition was complete, the cooling bath was removed and the mixture was stirred at ambient temperature for 18-24 h. The mixture was then externally cooled with ice and carefully treated with 2.50 parts of aqueous 1 N HCl, during which period an initial exotherm was observed accompanied by gas evolution. During the addition, the temperature climbed from -5° C. to 9° C. at which point 3.75 parts of water and 3.75 parts of ethyl acetate were added. The phases were vigorously mixed and separated. The aqueous phase was removed and extracted with 1.25 parts of ethyl acetate. The organic phases were combined and washed with 2.50 parts of brine. The organic phase was then washed with 2.50 parts of saturated aqueous sodium bicarbonate followed by 1.25 parts of brine. The organic layer was then dried over 0.6 parts of sodium sulfate, filtered, and concentrated in vacuo to a thick residue. The residue was then concentrated three times from 1.90 parts each of methanol. The resulting semi-solid material was then dissolved in 3.5 parts of hot toluene and concentrated while warming to 50-80° C., removing 2-3 parts of toluene. The resulting toluene solution was then filtered hot and allowed to crystallize with stirring for 18-48 h at ambient temperature, then 12-24 h at 0-4° C. The white crystalline material was isolated by suction filtration. After drying, the yield of 2-fluoro-2-phenyl-1,3-propanediol was 85-90% of theoretical. HPLC analysis typically shows >98% (AUC) F-Diol along with 0.5-1.1% defluorinated material (2-phenyl-1,3-propanediol (“Diol”)). 1H-NMR (d6-DMSO, 500 MHz) δ 7.40-7.20 (m, 5 H, PhH), 5.0 (t, 2 H, OH), 3.83-3.70 (m, 4 H, CH2). Under the HPLC conditions described for Example 2, the retention times were: Diol (8.1 min), F-Diol (8.5 min).
Stage #1: α-fluorophenylmalonate dipotassium salt With diborane In tetrahydrofuran at 20℃; Stage #2: With hydrogenchloride In water 3 2-Fluoro-2-phenyl-1,3-propanediol (F-Diol) To 14.4 parts of a 1 M solution of diborane in THF solution (1.15 L, 4 eq) was added 1.00 parts of F-K2PMA slowly at ambient temperature. Gas evolution was observed during the addition. The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was then externally cooled with an ice bath (typically, the reaction mixture is kept at a temperature of from 2-5° C. for 12-6 h) and was carefully treated with 6.25 parts of methanol. Solvents were removed under reduced pressure to leave a white paste, which was treated with 3.12 parts of 10% aqueous HCl solution followed by 6.88 parts of water. This aqueous mixture was washed with hexane, then saturated with NH4Cl, followed by extraction with ethyl acetate (EtOAc). The combined EtOAc solution was washed with brine, followed by saturated aqueous NaHCO3 solution, brine, and dried over anhydrous MgSO4. After removal of solvent, crude F-Diol was obtained as a pale yellow solid in 74% weight yield. NMR analysis was consistent with the structure of F-Diol with about 2-3% of defluorinated material (2-phenyl-1,3-propanediol (“Diol”)). Under the following HPLC conditions, the retention times were: F-Diol (5.8 min), Diol (6.2 min). Column: Kromasil C4, 5 μm, 25 cm × 4.6 mm Mobile phase:THF/MeOH/H2O = 3.5/20.0/76.5 (v/v) Flow rate: 1.5 mL/min (nominal) Detector: UV 210 nm Injection volume: 20 μL (nominal) Column temperature: 35 +/- 1° C. Run time: 20 min
  • 46
  • [ 108-05-4 ]
  • 1,2-dibromomethyl acetate [ No CAS ]
  • 2-bromomethyl-5-phenyl-1,3-dioxane [ No CAS ]
  • [ 1570-95-2 ]
  • [ 105-53-3 ]
  • [ 103486-56-2 ]
YieldReaction ConditionsOperation in experiment
With bromine In tetrachloromethane 24 Tetraethyl 2-(5-phenyl-1,3-dioxane-2-yl-methyl)-1,3-propylidenediphosphonate STR33 EXAMPLE 24 Tetraethyl 2-(5-phenyl-1,3-dioxane-2-yl-methyl)-1,3-propylidenediphosphonate STR33 Following the procedure described by Bedoukian (Journal of American Chemical Society, Vol. 66, p. 651, 1944) 2-bromomethyl-5-phenyl-1,3-dioxane was synthesised by reacting 1,2-dibromomethyl acetate (obtained by reacting vinyl acetate with bromine in carbon tetrachloride) with 2-phenyl-1,3-propanediol (obtained by reduction of diethyl phenyl malonate with LiAlH4). 2-bromomethyl-5-phenyl-1,3-dioxane was condensed with diethyl malonate to give the corresponding substituted malonate that was reduced to 2-(5-phenyl-1,3-dioxane-2-yl-methyl)-1,3-propanediol by LiAlH4 in diethyl ether such as described in example 23. Tosylation was carried out by the usual tosyl chloride/pyridine procedure. A solution of the ditosylate of 2-(5-phenyl-1,3-dioxane-2-yl-methyl)-1,3-propanediol (4.5 g, 80 mmol) in 20 ml dioxane was reacted at room temperature for 15 hours with a solution of 20 mmol sodium diethyl phosphite in 20 ml tetrahydrofuran.
  • 47
  • 2-phenyl-trimethylenesulfite [ No CAS ]
  • [ 1570-95-2 ]
  • tetra(n-butyl)ammonium hydrogen sulfate [ No CAS ]
  • [ 62822-77-9 ]
YieldReaction ConditionsOperation in experiment
With potassium permanganate; thionyl chloride In 2-phenyltrimethylensulfite; dichloromethane; water 8 EXAMPLE 8 EXAMPLE 8 12.5 Parts of thionyl chloride are slowly added to a boiling solution of 15.2 parts of 2-phenyl-1,3-propanediol in 30 parts of methylene chloride. The reaction mixture is refluxed for 30 minutes and then distilled in vacuo and 2-phenyltrimethylensulfite (b.p. 136°-40° C./3.5) is collected. 9.5 Parts of 2-phenyl-trimethylenesulfite are dissolved in 20 parts of methylene chloride and added while stirring to a mixture consisting of 7.9 parts of potassium permanganate, 40 parts of water, 25 parts of methylene chloride and 0.1 parts of tetrabutylammonium hydrogen sulphate, while the temperature is kept between 25° and 35° C. Stirring is continued for 15 minutes and the reaction mixture is filtered. The filtrate is decolorized with sodium hydrogen sulphite and separated. The organic phase is dried over anhydrous sodium sulphate and evaporated to dryness in vacuo. The residue consists of 2-phenyl-trimethylene sulphate (m.p. 79°-81° C.).
  • 48
  • [ 5428-02-4 ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
In methanol; hydrogen; toluene 4 2-Phenyl-1, 3-Propanediol EXAMPLE 4 2-Phenyl-1, 3-Propanediol 12 g. (0.06 mole) of 2-nitro-2-phenyl-1, 3-propanediol, 400 mg. of 5% palladium on calcium carbonate and 150 ml. of methanol are placed in a Parr hydrogenator bottle and reduced with hydrogen overnight. The mixture is filtered through Celite, concentrated to an oil and recrystallized from 30 ml. of toluene. The yield is 7.4 g. (80%) of product, M.P. 52°-4° C.
  • 49
  • [ 105-53-3 ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
With lithium aluminium tetrahydride In diethyl ether at 0 - 20℃; for 12h; Heating / reflux; 3.A A cooled (0 0C) suspension of lithium aluminum hydride (1.61g, 0.021 mol) in anhydrous ether (80 mL) was treated dropwise with diethyl malonate (5g, 0.021 mol) under an atmosphere of nitrogen. The mixture was allowed to warm to room temperature, stirred for 1O h and refluxed for an additional 2 h. The reaction was quenched with 20% aqueous NaOH (5 mL), the inorganic substances removed by filtration and organic layer was separated, washed with brine (30 mL), dried (MgSO4), filtered and concentrated. The title compound was obtained after flash column on silica gel using EtOAcrhexane 50:50 as the elute. lH NMR (CDCI3, 500 MHz) δ 7.41-7.21 (m, 5H), 4.05 (dd, J= 7.5, 3.2 Hz, 2H), 3.97 (dd, J= 5.8, 5.2 Hz, IH), 3.12 (m, IH).
  • 50
  • [ 1570-95-2 ]
  • [ 98-59-9 ]
  • [ 75590-25-9 ]
YieldReaction ConditionsOperation in experiment
35% With dmap In dichloromethane at 0℃; 70.b.i To a solution of 2-phenyl-1,3-propanediol (5 g, 32.9 mmol) and Et3N (5.5 ml_, 39.5 mmol) in DCM (164 ml_) at 0 0C were added tosyl chloride (6.3 g, 32.9 mmol) and DMAP (400 mg, 3.29 mmol). After 30 min, the solution was concentrated and purified via column chromatography (silica, 0.5-2% MeOH in DCM) yielding 3-hydroxy-2-phenylpropyl 4-methylbenzenesulfonate (3.5 g, 35%) as a white solid: LCMS m/z 307 (M+H)+.
  • 51
  • [ 33315-63-8 ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
92% With sodium tetrahydroborate; bromine In 1,2-dimethoxyethane at -10 - 20℃; for 0.5h;
  • 52
  • [ 672-13-9 ]
  • [ 1570-95-2 ]
  • [ 1079921-26-8 ]
YieldReaction ConditionsOperation in experiment
74% With toluene-4-sulfonic acid; orthoformic acid triethyl ester In dichloromethane at 20℃;
  • 53
  • [ 1570-95-2 ]
  • [ 2612-32-0 ]
YieldReaction ConditionsOperation in experiment
55% With platinum(IV) oxide; hydrogen; acetic acid for 24h;
  • 54
  • [ 1570-95-2 ]
  • [ 769-78-8 ]
  • (S)-3-hydroxy-2-phenylpropyl benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With (S,S)-2,6-bis{2-[hydroxy(biphenyl-4-yl)methyl]pyrrolidin-1-ylmethyl}-4-methylphenol; diethylzinc In toluene at -15℃; Inert atmosphere; optical yield given as %ee;
  • 55
  • [ 1570-95-2 ]
  • [ 67168-95-0 ]
YieldReaction ConditionsOperation in experiment
85% With pyridine; p-toluenesulfonyl chloride at 100 - 110℃;
  • 56
  • [ 1570-95-2 ]
  • [ 917-61-3 ]
  • [ 25451-15-4 ]
YieldReaction ConditionsOperation in experiment
With trifluoroacetic acid In toluene at 10 - 45℃; for 6h; Reflux; III A mixture of 120 kg of 2-phenyl- 1,3 -propanediol, 132 kg of sodium cyanate and 600 L of toluene was charged into a reactor and heated to 45 °C followed by the addition of 400 kg of trichloroacetic acid. The reaction mixture was stirred for 1 hr at 45°C and then was brought to reflux for 4 hr. The reaction mixture was cooled to room temperature and then to 10°C for 1 hr with stirring. Solids particles were filtered out and the remaining solution cake was washed with water in order to get a pH of at least 8. The obtained wet crude Felbamate was purified by crystallization form Methanol and was dried in a vacuum oven to yield Felbamate with at least 99% purity
  • 57
  • [ 1570-95-2 ]
  • [ 1710-98-1 ]
  • C20H24O3 [ No CAS ]
  • [ 1354780-97-4 ]
  • [ 1354781-03-5 ]
YieldReaction ConditionsOperation in experiment
19% With C23H24NOP; N-ethyl-N,N-diisopropylamine In toluene at 0℃; for 7h; Molecular sieve; Inert atmosphere; optical yield given as %ee; enantioselective reaction;
  • 58
  • [ 1570-95-2 ]
  • [ 1123-85-9 ]
YieldReaction ConditionsOperation in experiment
72% With methanol; potassium <i>tert</i>-butylate; C37H36Cl2NPRuS2 at 135℃; for 36h; Sealed tube; Inert atmosphere; Green chemistry;
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 1 h / Reflux 1.2: 16 h / Reflux 2.1: dichloro(benzene)ruthenium(II) dimer; N,N-diisopropylimidazolium bromide; sodium hydride / toluene; acetonitrile / 24 h / Reflux
78 %Spectr. With trimethylamine-N-oxide; (1,4-dimethyl-5,7-diphenyl-1,2,3,4-tetrahydro-6H-cyclopenta[b]pyrazin-6-one) irontricarbonyl complex3; sodium hydroxide In methanol at 130℃; for 24h;
  • 59
  • [ 1570-95-2 ]
  • [ 100-39-0 ]
  • [ 189886-53-1 ]
YieldReaction ConditionsOperation in experiment
69% With dibenzo[c,e][1,2]oxaborinin-6-ol; N-ethyl-N,N-diisopropylamine In acetonitrile at 25℃; for 24h;
56% Stage #1: 2-phenylpropane-1, 3-diol With sodium hydride In tetrahydrofuran for 1h; Reflux; Stage #2: benzyl bromide In tetrahydrofuran for 16h; Reflux;
  • 60
  • [ 1570-95-2 ]
  • [ 98-59-9 ]
  • [ 1570-96-3 ]
YieldReaction ConditionsOperation in experiment
18% Stage #1: 2-phenylpropane-1, 3-diol; p-toluenesulfonyl chloride With trimethylamine hydrochloride; triethylamine In acetonitrile at 0℃; for 5h; Inert atmosphere; Stage #2: With N,N`-dimethylethylenediamine In acetonitrile 4.2.29 2-(4-Methoxyphenyl)-5-phenyl-1,3-dithiane (1aa) Under an Ar atmosphere, diethyl phenylmalonate (4.5 g, 19.0 mmol) was added dropwise to a solution of LiAlH4 (1.9 g, 50.0 mmol) in THF (90 mL) at 0°C. The reaction mixture was warmed up to room temperature and stirred overnight. After the addition of Na2SO4, the mixture was extracted with AcOEt (30mL×3) and the combined organic layer was washed with H2O (50mL×2) and brine (50mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (eluent: hexane/AcOEt=1:3) to give 2-phenyl-1,3-propanediol (0.85 g, 28%) as colorless oil. Under an Ar atmosphere, a solution of p-toluenesulfonyl chloride (6.0 g, 31.5 mmol) in MeCN (16mL) was added dropwise to a solution of 2-phenyl-1,3-propanediol (1.6g, 10.5mmol), Me3N·HCl (0.20g, 2.1mmol), and Et3N (3.2g, 31.5mmol) in MeCN (7mL) at 0°C and stirred for 5h at the same temperature. After the addition of N,N′-dimethylethylenediamine (2mL), the mixture was extracted with AcOEt (30mL×3) and the combined organic layer was washed with H2O (50mL×2) and brine (50mL×1). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (eluent: hexane/AcOEt=3:1) to give 2-phenyl-1,3-propaneditosylate (0.88g, 18%) as a colorless solid. Under an Ar atmosphere, thiourea (1.4g, 19.0mmol) was added to a solution of 2-phenyl-1,3-propaneditosylate (0.88g, 1.9mmol) in EtOH (10mL) at room temperature, and the mixture was heated under reflux overnight. After the reaction mixture was cooled down to room temperature, 20% NaOH (10mL) was added and the whole mixture was heated under reflux overnight. After the addition of 1M HCl (30mL), the mixture was extracted with CH2Cl2 (50mL×3) and the combined organic layer was washed with H2O (50mL×1) and brine (50mL×1). The organic layer was dried over MgSO4 and concentrated in vacuo to give 2-phenyl-1,3-propanedithiol (0.48g) as yellowish oil, which was used to the next reaction without further purification. According to the Method A, 1aa was prepared from the above-obtained 2-phenyl-1,3-propanedithiol and p-anisaldehyde (0.27 g, 75% over two steps). Recrystallized from AcOEt, colorless needles, mp 165-167°C. IR (neat): 2892, 1605, 1509, 1248, 1170, 1022, 851, 818, 767, 725cm-1. 1H NMR (400MHz, CDCl3/TMS) δ (ppm): 2.92-2.96 (m, 2H), 3.16-3.30 (m, 3H), 3.80 (s, 3H), 5.22 (s, 1H), 6.88 (d, J=8.8Hz, 2H), 7.22-7.27 (m, 3H), 7.32-7.36 (m, 2H), 7.44 (d, J=8.8Hz, 2H). 13C{1H} NMR (100MHz, CDCl3) δ (ppm): 38.3, 42.8, 50.4, 44.3, 114.2, 126.7, 127.1, 128.87, 128.92, 130.3, 144.9, 159.7. LRMS (EI) m/z: 302 (M+). HRMS: calcd for C17H18OS2: 302.0799, found: 302.0780.
  • 61
  • [ 1570-95-2 ]
  • [ 106-95-6 ]
  • [ 1616561-74-0 ]
YieldReaction ConditionsOperation in experiment
46% Stage #1: 2-phenylpropane-1, 3-diol With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.166667h; Inert atmosphere; Stage #2: allyl bromide In tetrahydrofuran at 0 - 20℃; for 5h;
  • 62
  • [ 124-38-9 ]
  • [ 1570-95-2 ]
  • [ 857193-29-4 ]
YieldReaction ConditionsOperation in experiment
62% With 2-Cyanopyridine; cerium(IV) oxide at 169.84℃; for 2h; Autoclave;
53 %Chromat. With 1-bromo-butane; 3-benzyl-5-(2-hydroxy-ethyl)-4-methyl-thiazolium betaine; caesium carbonate In N,N-dimethyl-formamide at 90℃; for 24h; Glovebox; Schlenk technique;
  • 63
  • [ 1570-95-2 ]
  • [ 1125-88-8 ]
  • trans-2,5-diphenyl-1,3-dioxane [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With zinc(II) chloride In chloroform at 20℃; Inert atmosphere;
  • 64
  • [ 1570-95-2 ]
  • [ 2186-92-7 ]
  • trans-2-(4-methoxyphenyl)-5-phenyl-1,3-dioxane [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With zinc(II) chloride In chloroform at 20℃; Inert atmosphere;
  • 65
  • [ 1570-95-2 ]
  • [ 3395-81-1 ]
  • trans-2-(4-chlorophenyl)-5-phenyl-1,3-dioxane [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With zinc(II) chloride In chloroform at 20℃; Inert atmosphere;
  • 66
  • [ 1570-95-2 ]
  • [ 33250-32-7 ]
  • [ 475145-42-7 ]
YieldReaction ConditionsOperation in experiment
75% With zinc(II) chloride In chloroform at 20℃; Inert atmosphere;
  • 67
  • [ 1570-95-2 ]
  • [ 990-91-0 ]
  • 3-di(benzyloxy)phosphoryloxy-2-phenyl-1-propanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere; chemoselective reaction; General procedure for the phosphorylation of diols. General procedure: The diol (0.49 mmol) was dissolved in 1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to the solution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol). Ti(OtBu)4 (19 μL, 0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. To quench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2 mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate was concentrated under reduced pressure. The crude product was purified using silica gel chromatography.
81% With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere; General Procedure for the Phosphorylation of Diols General procedure: The diol (0.49 mmol) was dissolved in1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to thesolution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol;). Ti(OtBu)4 (19 μL,0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. Toquench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate wasconcentrated under reduced pressure. The crude product was purified using silica gelchromatography.
  • 68
  • [ 1570-95-2 ]
  • [ 37504-67-9 ]
  • 69
  • [ 1570-95-2 ]
  • [ 133059-43-5 ]
  • C16H14BrFO2 [ No CAS ]
  • C16H14BrFO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 210 mg 2: 70 mg With toluene-4-sulfonic acid In toluene for 24h; Reflux; Dean-Stark; 144 A mixture of 1 ,3-dihydroxypropane 170 (340 mg, 2 mmol, 1.0 equiv.), 4-bromo-3-fluorobenzaldehyde 169 (450 mg, 2 mmol, 1.0 equiv.), and p-toluenesulfonic acid (0.1 g, 0.25 equiv.) in toluene (30 mE) was refluxed for 24 h with a Dean-Stark trap attached for removal of water. The mixture was diluted with EtOAc, washed with sat. sodium bicarbonate and brine, dried and concentrated. The crude mixture was purified on a silica gel column (5-20% EtOAc in hexane) to give major isomer 171 (210 mg) and minor isomer 172 (70 mg). Compound 173 was synthesized from 171 according to Method 1. [M-H]=301.1 mlz.Activity:A
  • 70
  • [ 1570-95-2 ]
  • [ 536-90-3 ]
  • 7-methoxy-3-phenylquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With tetrafluoroboric acid diethyl ether; [(PCy3)(CO)RuH]4(μ-O)(μ-OH)2}; cyclopentene In 1,4-dioxane at 140℃; for 14h; Sealed tube; Schlenk technique; Inert atmosphere; regioselective reaction;
  • 71
  • [ 1570-95-2 ]
  • [ 134-32-7 ]
  • [ 50781-37-8 ]
YieldReaction ConditionsOperation in experiment
56% With tetrafluoroboric acid diethyl ether; [(PCy3)(CO)RuH]4(μ-O)(μ-OH)2}; cyclopentene In 1,4-dioxane at 130℃; for 14h; Sealed tube; Schlenk technique; Inert atmosphere; regioselective reaction;
  • 72
  • [ 1570-95-2 ]
  • [ 87-59-2 ]
  • [ 1373117-74-8 ]
YieldReaction ConditionsOperation in experiment
60% With tetrafluoroboric acid diethyl ether; [(PCy3)(CO)RuH]4(μ-O)(μ-OH)2}; cyclopentene In 1,4-dioxane at 130℃; for 14h; Sealed tube; Schlenk technique; Inert atmosphere; regioselective reaction;
  • 73
  • [ 1570-95-2 ]
  • [ 14268-66-7 ]
  • 7-phenyl-[1,3]dioxolo[4,5-g]quinoline [ No CAS ]
  • C16H17NO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 63% 2: 22% With tetrafluoroboric acid diethyl ether; [(PCy3)(CO)RuH]4(μ-O)(μ-OH)2}; cyclopentene In 1,4-dioxane at 140℃; for 14h; Sealed tube; Schlenk technique; Inert atmosphere; regioselective reaction;
  • 74
  • [ 1570-95-2 ]
  • [ 10272-07-8 ]
  • C17H15NO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With tetrafluoroboric acid diethyl ether; [(PCy3)(CO)RuH]4(μ-O)(μ-OH)2}; cyclopentene In 1,4-dioxane at 150℃; for 14h; Sealed tube; Schlenk technique; Inert atmosphere; regioselective reaction;
  • 75
  • [ 1570-95-2 ]
  • [ 59276-34-5 ]
  • C18H20O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With toluene-4-sulfonic acid In dichloromethane at 20℃; for 7h; Inert atmosphere;
  • 76
  • C18H21NO2 [ No CAS ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
89% In methanol for 0.5h; UV-irradiation;
  • 77
  • [ 1570-95-2 ]
  • [ 57-13-6 ]
  • [ 25451-15-4 ]
YieldReaction ConditionsOperation in experiment
61% With iron(II) bromide In 1,4-dioxane at 150℃; for 6h; Inert atmosphere; Sealed tube;
at 145℃; for 8h; 6 H2NC(0)0CH2CH(Ph)CH20C(0)NH210 Using the procedure reported in Example 5, 2-phenyl- 1,3 -propanediol was converted into felbamate in one step. 0.300 g of 2-phenyl- 1,3 -propanediol were reacted with (0066) 0.230 g of urea (1 :2 molar ratio) for 8 h at 145°C K. At the end the viscous orange solution was cooled to room temperature and extracted with tetrahydrofuran that extracted the products and left behind the excess solid urea. The THF solution was analyzed by analytical HPLC and showed to contain the starting unreacted product (20-30%, based on different tests), the monocarbamate (10-15 %) and the dicarbamate (60-65%). The latter was isolated by preparative HPLC and characterized by FTIR and 'H and 13C NMR. (0067) FTIR: v(C=0)= 1734 cm 1 (0068) NMR (CDCh): CH2-0 4.73; CCHC 2.776; CeHs 0-7.242, m-7.255, p-7.132; NF/25.4 ppm. (0069) 13C NMR (DMSO-de): CH2-C(H)(Ph)-CH2 40.8; CH2 69.8; CPh,„ 127.7; CPh,m 128.5; CPh,p 128.8; CPh-C 141.1; C=0 157.2 ppm.
  • 78
  • [ 17838-69-6 ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
99.11% With sodium tetrahydroborate In ethyl acetate; toluene at 50 - 55℃; 3.4 Example 3 (4) The ethyl α-formylphenylacetate, silicate activator and sodium borohydride prepared above were added to a mixed solvent of ethyl acetate and toluene, and the mixture was uniformly mixed and transferred to a three-necked flask and slowly heated up to 50-55°C, reaction 1-2h,After the reaction is completed, the mixture is cooled to room temperature, and then the solvent is removed under reduced pressure. Toluene is added to the concentrate, stirred, and the layers are separated. The aqueous layer is extracted twice with toluene, and the toluene solution is combined. The toluene solution is washed with saturated brine and dried. Remove the solvent under reduced pressure2-phenyl-1,3-propanediol was obtained with a yield of 99.11%;Among them, the molar ratio of ethyl α-formylbenzeneacetate and sodium borohydride was 1:1.7; the mass ratio of sodium borohydride and silicate activator was 1:0.4.
  • 79
  • [ 463-58-1 ]
  • [ 1570-95-2 ]
  • C10H10O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
77.3% With lithium carbonate; zinc(II) oxide In acetonitrile at 150℃; for 12h; Autoclave; 6 Example 6 Into a 10 ml capacity autoclave were added several masses of 2-phenyl-1,3-propanediol, acetonitrile, and pressure.Lithium carbonate/zinc oxide, the mass ratio of catalyst to diol was 10:100, and the mass ratio of acetonitrile to diol was 10:1. thenThe reaction vessel was closed and carbon oxysulfide gas was introduced to the specified pressure. The molar ratio of carbon oxysulphide to diol was 8:1.Place in a 150°C oil bath and react under autogenous pressure for 12 hours. After the reaction is completed, it is cooled to room temperature and the air is released.The nuclear magnetic spectrum was used to calculate the yield. The test results are shown in Table 1.
  • 80
  • [ 1570-95-2 ]
  • [ 97-72-3 ]
  • (S)-3-hydroxy-2-phenylpropyl isobutyrate [ No CAS ]
  • 2-phenylpropane-1,3-diyl bisisobutylate [ No CAS ]
  • C13H18O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
56 % ee With N,N,N,N,-tetramethylethylenediamine; C53H40N2O2 In tetrahydrofuran; toluene at -60℃; for 7h; enantioselective reaction; General procedure for the desymmetrization of 1,3-diols with catalyst 1a under the optimal conditions General procedure: To a solution of catalyst 1a (0.1mol %), substrate 2a-n (1.0 equiv), and TMEDA (1.5 equiv) in dry toluene(0.2 M) was added (i-PrCO)2O (1.1 equiv) at -60 °C. The reaction mixture was added MeOH (2 mL) to quenchthe reaction and stirred for 30 min at room temperature. The resulting solution was added H2O (10 mL), thenextracted with Et2O (10 mL×3), dried over MgSO4, and concentrated in vacuo to give the crude mixture. Thepurification of the crude product by flash column chromatography on silica gel (eluent: hexane/Et2O = 2:1 toEt2O, v/v or hexane/EtOAc = 1:1, v/v) gave the monoacylate 3a-n, diacylate 4a-n and recovery of substrate2a-n. The enantiomeric ratios were determined by HPLC analysis
  • 81
  • [ 1570-95-2 ]
  • [ 97-72-3 ]
  • 2-phenylpropane-1,3-diyl bisisobutylate [ No CAS ]
  • C13H18O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; triethylamine In dichloromethane Racemic sample of monoacylate and diacylatewere synthesized by general acylation method with 5 mol % of DMAP, 1.5 equiv of (i-PrCO)2O, and 1.5 equivof Et3N in CH2Cl2.
  • 82
  • [ 1570-95-2 ]
  • [ 625095-59-2 ]
  • C22H29N6O4P [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine; triethylamine In dichloromethane at -78 - -70℃; 1 Preparation of 9-[2-(2-phenyl)-2-oxa-1,3,2-dioxaphosphazyl-2-methyleneoxyethyl]adenine (Compound 1) PMEA (3.00 g, 10.99 mmol) was suspended in dry dichloromethane (40 mL), then N,N-diethylformamide (1.35 ml, 12.12 mmol). After stirring, oxalyl chloride (3.5 ml, 36.80 mmol) was slowly added dropwise. After the dropwise addition was completed, the mixture was refluxed for 2 hours, cooled to room temperature and concentrated under reduced pressure. Dry dichloromethane (40 ml) was added to the residue, which was evaporated and evaporated. Additional dry dichloromethane (40 ml) was added. Pyridine (1.08 ml, 13.42 mmol) was slowly added under ice-cooling and stored under the conditions, and was taken. 2-Phenyl-1,3-propanediol (1.672g, 10.97mmol), triethylamine (7.5ml, 53.96mmol), dissolved in dry dichloromethane (30ml), liquid nitrogen-acetone bath, reaction liquid cooling To -78 ° C, then slowly add the above backup solution, At the time of dropping, the temperature of the control system was maintained at -70 ° C, and after the completion of the dropwise addition, the temperature was maintained for 1 hour, and then the reaction was carried out under ice bath conditions. The reaction solution was washed with water (50 ml) 3 times. The organic layer was dried over anhydrous MgSO 4 for 3 h. Filtered, the filtrate was concentrated, The residue was subjected to silica gel column chromatography (mobile phase: CH2Cl2: CH3OH = 10:1) was isolated and purified to a yellow oil.
  • 83
  • [ 1570-95-2 ]
  • [ 7766-23-6 ]
  • 3-(3-bromo-2-methylphenoxy)-2-phenylpropan-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
54.8% With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 15℃; for 15h; Inert atmosphere; 25.a (a) 3-(3-bromo-2-methyl-phenoxy)-2-phenyl-propan-l-ol. To a solution of 3-bromo-2-methyl-phenol (12.75 g, 68.17 mmol) in THF (50 mL) was added 2-phenylpropane-l,3-diol (12.45 g, 81.80 mmol) and DIAD (20.68 g, 102.25 mmol, 19.88 mL). After that, PPh3(35.76 g, 136.34 mmol) was added at 0 °C. The mixture was stirred at 15 °C for 15 h. The reaction mixture was diluted with water (40mL) and extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (3 x 30 mL), dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO; 40 g SEPAFLASH Silica Flash Column, Eluent of 0-100% Ethyl acetate/Petroleum ethergradient 50 mL/min) to give 3-(3-bromo-2-methyl-phenoxy)-2- phenyl-propan-l-ol (12 g, 37.36 mmol, 54.80% yield) as a white solid. 1H NMR (400 MHz,CDCI3) d 7.36-7.28 (m, 5H), 7.16-7.14 (m, 1H), 6.98 (m, 1H), 6.79-6.77 (m, 1H), 5.01-4.95 (m, 1H), 4.26-4.21 (m, 2H), 4.20 (m, 2H), 4.11-4.02 (s, 1H), 3.77-3.35(m, 1H), 2.27 (m, 3H).
  • 84
  • C18H38OSi4 [ No CAS ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
88% Stage #1: C18H38OSi4 With tetrabutyl ammonium fluoride In dihydrogen peroxide at 20℃; Stage #2: With potassium hydrogencarbonate In methanol at 65℃;
  • 85
  • [ 108-86-1 ]
  • [ 1570-95-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: iridium(lll) bis[2-(2,4-difluorophenyl)-5-methylpyridine-N,C20]-4,40-di-tert-butyl-2,20-bipyridine hexafluorophosphate; sodium carbonate; 4,4'-di-tert-butyl-2,2'-bipyridine; bis(1,5-cyclooctadiene)nickel (0) / 1,4-dioxane / 12 h / 20 °C / Irradiation 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 0 °C 3.1: tetrabutyl ammonium fluoride / dihydrogen peroxide / 20 °C 3.2: 65 °C
  • 86
  • [ 1570-95-2 ]
  • [ 6609-64-9 ]
  • C13H18O8P2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% Stage #1: 2-phenylpropane-1, 3-diol In dichloromethane at 20℃; for 0.5h; Stage #2: 2-Chloro-2-oxo-1,3,2-dioxaphospholane In dichloromethane at 0 - 20℃; for 12h; 22 Example 22 Preparation of compound 21 (bis(2-oxo-1,3,2-dioxaphosphorane) 2-phenyl-1,3-propanediol ester): Add 400g of methylene chloride and 152g of 2-phenyl-1,3-propanediol (Reactant C) to a 1000ml three-necked flask at room temperature, and stir at room temperature for 0.5h,The solution was colorless and transparent. The three-necked bottle was connected to an external gas absorption device, and then 300 g of Compound B prepared in Example 1 was slowly added to a 1000-ml three-necked bottle via a dropping funnel.Control the drop acceleration to 1 drop/second, the reaction temperature is 0 , with the addition of Compound B, a lot of heat is released and a lot of HCl gas is released,After all drops were completed, the solution was colorless and transparent, and then the reaction was slowly raised to room temperature and stirring was continued for 12h.Dichloromethane was removed by atmospheric distillation to obtain a pale yellow solid, and the pale yellow solid was crystallized using ethanol to obtain 338 g of a white solid with a yield of 93%.This product is compound 21 (bis(2-oxo-1,3,2-dioxaphosphorane) 2-phenyl-1,3-propanediol ester),
  • 87
  • [ 1570-95-2 ]
  • [ 822-39-9 ]
  • C13H18O6P2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% In dichloromethane at 0 - 20℃; for 12h; 22 Preparation of compound 21 (bis(1,3,2-dioxaphospholan) 2-phenyl-1,3-propanediol ester) Add 400g of dichloromethane and 152g of 2-phenyl-1,3-propanediol (reactant C) to a 1000ml three-necked flask at room temperature. Stir at room temperature for 0.5h. The solution is colorless and transparent. The three-necked flask is connected to an external gas absorption device. Subsequently, 300g of compound B prepared in Example 1 was slowly added to a 1000ml three-necked flask via a dropping funnel, the dropping rate was controlled to 1 drop/sec, and the reaction temperature was 0°C. With the dropping of compound B, a large amount of heat was released and A large amount of HCl gas is released, and the solution is colorless and transparent after all the drops are completed. Then the reaction is slowly raised to room temperature and stirring is continued for 12 hours. The dichloromethane is distilled off under normal pressure to obtain a pale yellow solid. The pale yellow solid is crystallized from ethanol. The white solid is 309 g, and the yield is 93%.The product is compound 21 (bis(1,3,2-dioxaphospholane) 2-phenyl-1,3-propanediol ester),
  • 89
  • [ 1570-95-2 ]
  • [ 939-99-1 ]
  • (S)-2-phenyl-3-(p-trifluoromethylbenzyloxy)propan-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With (R)-2,4-dimethyl-7-(2-(trityloxy)naphthalen-1-yl)-5H-benzo[c]naphtho[2,3-e][1,2]oxaborinin-5-ol; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 24h; Sealed tube; enantioselective reaction;
  • 90
  • [ 1570-95-2 ]
  • [ 2506-41-4 ]
  • (S)-3-(naphthalen-2-ylmethoxy)-2-phenylpropan-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With (R)-2,4-dimethyl-7-(2-(trityloxy)naphthalen-1-yl)-5H-benzo[c]naphtho[2,3-e][1,2]oxaborinin-5-ol; potassium carbonate; potassium iodide In acetonitrile at 20℃; for 24h; Sealed tube; enantioselective reaction;
  • 91
  • [ 1570-95-2 ]
  • [ 100-44-7 ]
  • [ 189886-53-1 ]
YieldReaction ConditionsOperation in experiment
65% With dibenzo[c,e][1,2]oxaborinin-6-ol; potassium carbonate; potassium iodide In acetonitrile at 25℃; for 24h;
  • 92
  • [ 485-47-2 ]
  • [ 1570-95-2 ]
  • (Z,Z)-5,5''-diphenyl-2'H-dispiro[[1,3]dioxane-2,1'-indene-3',2''-[1,3]dioxan]-2'-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With toluene-4-sulfonic acid In toluene for 16h; Inert atmosphere; Reflux; Dean-Stark;
  • 93
  • [ 1570-95-2 ]
  • [ 100-63-0 ]
  • [ 15132-01-1 ]
YieldReaction ConditionsOperation in experiment
78% With triruthenium dodecacarbonyl; C32H34N3P2(1+)*Cl(1-); anhydrous Sodium acetate In o-dimethylbenzene at 130℃; for 24h; Inert atmosphere;
Same Skeleton Products
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Chemical Structure| 83811-73-8

[ 83811-73-8 ]

(4-Phenylcyclohexyl)methanol

Similarity: 0.89

Chemical Structure| 15100-35-3

[ 15100-35-3 ]

Bicyclo[4.2.0]octa-1,3,5-trien-7-ylmethanol

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Chemical Structure| 5406-86-0

[ 5406-86-0 ]

2-(4-(tert-Butyl)phenyl)ethanol

Similarity: 0.88

Chemical Structure| 22436-06-2

[ 22436-06-2 ]

(S)-2-Methyl-3-phenylpropan-1-ol

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Alcohols

Chemical Structure| 61826-40-2

[ 61826-40-2 ]

(2-Phenylcyclopropyl)methanol

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Chemical Structure| 83811-73-8

[ 83811-73-8 ]

(4-Phenylcyclohexyl)methanol

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Chemical Structure| 15100-35-3

[ 15100-35-3 ]

Bicyclo[4.2.0]octa-1,3,5-trien-7-ylmethanol

Similarity: 0.89

Chemical Structure| 5406-86-0

[ 5406-86-0 ]

2-(4-(tert-Butyl)phenyl)ethanol

Similarity: 0.88

Chemical Structure| 22436-06-2

[ 22436-06-2 ]

(S)-2-Methyl-3-phenylpropan-1-ol

Similarity: 0.88