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Product Details of [ 16606-55-6 ]

CAS No. :16606-55-6 MDL No. :MFCD00798265
Formula : C4H6O3 Boiling Point : -
Linear Structure Formula :- InChI Key :RUOJZAUFBMNUDX-GSVOUGTGSA-N
M.W : 102.09 Pubchem ID :641813
Synonyms :

Calculated chemistry of [ 16606-55-6 ]

Physicochemical Properties

Num. heavy atoms : 7
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.75
Num. rotatable bonds : 0
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 21.99
TPSA : 35.53 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) : -7.21 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.25
Log Po/w (XLOGP3) : -0.41
Log Po/w (WLOGP) : 0.54
Log Po/w (MLOGP) : -0.38
Log Po/w (SILICOS-IT) : 0.84
Consensus Log Po/w : 0.37

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.21
Solubility : 62.3 mg/ml ; 0.61 mol/l
Class : Very soluble
Log S (Ali) : 0.13
Solubility : 137.0 mg/ml ; 1.34 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : -0.16
Solubility : 70.5 mg/ml ; 0.69 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.2

Safety of [ 16606-55-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 UN#:N/A
Hazard Statements:H315-H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 16606-55-6 ]

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

  • Upstream synthesis route of [ 16606-55-6 ]
  • Downstream synthetic route of [ 16606-55-6 ]

[ 16606-55-6 ] Synthesis Path-Upstream   1~22

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YieldReaction ConditionsOperation in experiment
34.2% With C126H91CoN12O10; tetrabutyl-ammonium chloride In dichloromethane at 25℃; for 96 h; Autoclave General procedure: All reactions were conducted in a 100 mL stainless steel autoclave equipped with a magnetic stir bar, and submerged in anoil bath. The required catalyst, tetrabutylammonium chloride (TBAC) as the co‐catalyst, epoxide, and CH2Cl2 were added tothe reactor in turn. The reactor was then charged with CO2 and vented three times, and finally pressurized with CO2 to 1.0 MPa. The contents were then stirred at room temperature for an established period that depended on the selected substrate and catalyst, after which the reactor was carefully discharged to atmospheric pressure. The yield of cyclic carbonate was determinedby the subtraction method or by comparison betweenthe integral areas obtained by 1H NMR spectroscopy for thecyclic carbonate and epoxide.
31.6% With C126H91CoN12O10; tetrabutyl-ammonium chloride In dichloromethane at 25℃; for 96 h; Autoclave General procedure: All reactions were conducted in a 100 mL stainless steel autoclave equipped with a magnetic stir bar, and submerged in anoil bath. The required catalyst, tetrabutylammonium chloride (TBAC) as the co‐catalyst, epoxide, and CH2Cl2 were added tothe reactor in turn. The reactor was then charged with CO2 and vented three times, and finally pressurized with CO2 to 1.0 MPa. The contents were then stirred at room temperature for an established period that depended on the selected substrate and catalyst, after which the reactor was carefully discharged to atmospheric pressure. The yield of cyclic carbonate was determinedby the subtraction method or by comparison betweenthe integral areas obtained by 1H NMR spectroscopy for thecyclic carbonate and epoxide.
38.8 % ee at 25℃; for 25 h; Autoclave General procedure: A solution of freshly prepared SalenCo(III)Y (0.1 mmol) andepoxide (100 mmol) was introduced into a 100 mL stainless-steelautoclave, which was purged three times and charged with CO2to 1.2 MPa. The reaction mixture was stirred at room temperature.When the pressure of reactor was fall down to a presetting value, itwas then vented carefully. After removing the excess epoxide, theresidue was weighed to measure the conversion of epoxide, chiralcyclic carbonate (R = Me, Et, CH2Cl) was distilled under vacuum as asa colorless liquid or it (R = Ph, PhOCH2) was obtained by columnchromatography through a short silica–gel column to yield whitesolid product (ethyl acetate/petroleum ether = 5:1).
Reference: [1] Dalton Transactions, 2013, vol. 42, # 27, p. 9930 - 9937
[2] Chinese Journal of Catalysis, 2018, vol. 39, # 5, p. 997 - 1003
[3] Chinese Journal of Catalysis, 2018, vol. 39, # 5, p. 997 - 1003
[4] Journal of the American Chemical Society, 2004, vol. 126, # 12, p. 3732 - 3733
[5] Chemical Communications, 2004, # 14, p. 1622 - 1623
[6] Tetrahedron Letters, 2007, vol. 48, # 2, p. 297 - 300
[7] Tetrahedron Letters, 2008, vol. 49, # 46, p. 6589 - 6592
[8] Advanced Synthesis and Catalysis, 2009, vol. 351, # 9, p. 1325 - 1332
[9] Advanced Synthesis and Catalysis, 2009, vol. 351, # 9, p. 1325 - 1332
[10] Green Chemistry, 2009, vol. 11, # 7, p. 935 - 938
[11] Green Chemistry, 2009, vol. 11, # 7, p. 935 - 938
[12] Science China Chemistry, 2011, vol. 54, # 7, p. 1044 - 1050
[13] Science China Chemistry, 2011, vol. 54, # 7, p. 1044 - 1050
[14] Catalysis Science and Technology, 2013, vol. 3, # 10, p. 2661 - 2667
[15] Journal of Molecular Catalysis A: Chemical, 2016, vol. 411, p. 34 - 39
[16] RSC Advances, 2016, vol. 6, # 4, p. 3243 - 3249
[17] Chemical Communications, 2017, vol. 53, # 79, p. 10930 - 10933
[18] Chemical Communications, 2017, vol. 53, # 79, p. 10930 - 10933
[19] Chinese Journal of Catalysis, 2018, vol. 39, # 5, p. 997 - 1003
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YieldReaction ConditionsOperation in experiment
66.7 % ee at 25℃; for 8 h; Autoclave General procedure: Catalyst of (S,R,R,S)-ZSS-2b (631 mg, 0.1 mmol), cocatalyst of tetrabutylammonium fluoride (TBAF, 0.0522 g, 0.2 mmol), and racemic propylene oxide (PO, 7 mL, 100 mmol) were introduced into a 100-mL stainless steel autoclave to form a brown solution. The reactor was purged thrice with carbon dioxide, and charged it to 0.8 MPa. Then, the asymmetric catalytic reaction took place at room temperature. After some time, the pressure in the reactor decreased to an expected value, and it was vented to terminate the reaction. After removing the unreacted epoxide, chiral cyclic carbonate (R=Me, Et, CH2Cl), weighed to calculate the yield of cyclic carbonate, was distilled under vacuum as a colorless liquid or it (R=Ph, PhOCH2) was obtained by column chromatography through a short silica gel column (ethyl acetate:petroleum ether = 5:1).
Reference: [1] Tetrahedron Asymmetry, 2008, vol. 19, # 16, p. 1947 - 1953
[2] Catalysis Communications, 2016, vol. 81, p. 50 - 53
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YieldReaction ConditionsOperation in experiment
66.8 % ee at 0℃; for 8 h; Autoclave General procedure: Catalyst of (S,R,R,S)-ZSS-2b (631 mg, 0.1 mmol), cocatalyst of tetrabutylammonium fluoride (TBAF, 0.0522 g, 0.2 mmol), and racemic propylene oxide (PO, 7 mL, 100 mmol) were introduced into a 100-mL stainless steel autoclave to form a brown solution. The reactor was purged thrice with carbon dioxide, and charged it to 0.8 MPa. Then, the asymmetric catalytic reaction took place at room temperature. After some time, the pressure in the reactor decreased to an expected value, and it was vented to terminate the reaction. After removing the unreacted epoxide, chiral cyclic carbonate (R=Me, Et, CH2Cl), weighed to calculate the yield of cyclic carbonate, was distilled under vacuum as a colorless liquid or it (R=Ph, PhOCH2) was obtained by column chromatography through a short silica gel column (ethyl acetate:petroleum ether = 5:1).
Reference: [1] Catalysis Communications, 2016, vol. 81, p. 50 - 53
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Reference: [1] Organic Letters, 2006, vol. 8, # 20, p. 4401 - 4404
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Reference: [1] Organic Letters, 2006, vol. 8, # 20, p. 4401 - 4404
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YieldReaction ConditionsOperation in experiment
87% With sodium hydroxide In N,N-dimethyl-formamide at 90 - 140℃; for 12 h; Inert atmosphere To the reaction flask was added 200 ml of N, N-dimethylformamide (DMF)N2 protection,Adenine (30.0 g, 0.222 mol, 1 eq.) Was added,Stirring,NaOH (0.45 g, 0.011 mol) and was addedPropylene carbonate (28.5 g, 0.279 mol, 1.26 eq.),And the temperature was raised to 130 to 140 ° C.12 hours after the sampling test,When the adenine content in 1percent or less,The reaction can be stopped.The temperature slowly reduced to 90 below,200 ml of toluene,Continue to cool to 0 ~ 5 ,And the mixture was stirred for 2 hours.Filtered and dried to give 38.13 g of a white solid,Yield 87percent
87% With sodium hydroxide In N,N-dimethyl-formamide at 130 - 140℃; for 12 h; Inert atmosphere To the reaction flask was added 200 ml of N, N-dimethylformamide (DMF), protected with N2, added adenine (30.0 g, 0.222 mol, 1eq .), stirred, NaOH (0 · 45 g, mol) and R-propylene carbonate (28.5 g, 0. 279 mol, 1.3 eq.) and heated to 130 to 140 ° C. 12 hours after the sampling test, when the adenine content of 1percent or less, can stop the reaction. The temperature slowly drops below 90 ° C, add 200 ml of toluene, continue to cool to 0 ~ 5 ° C and stir for 2 hours. Filtered and dried to give 38.13 g of a white solid, 87percent yield,
81% With sodium hydroxide In N,N-dimethyl-formamide at 140℃; for 16 h; A solution of adenine (3.85g, 28.49 mmol) , (R) - propylene carbonate (2.7 mL, 31.34 mmol), and pulverized sodium hydroxide (60 mg, 1.42 mmol) in anhydrous DMF (80 mL) was heated at 1400C with stirring for 16 h. After cooling, the mixture was then filtered to remove insoluble materials, the filtrate was evaporated under reduced pressure and co-evaporated three times with toluene. The residue was triturated with EtOAc then filtered to give a white solid which was immediately recrystallized in ethanol to afford compound 7 (4.5 g, 81 percent) : mp 193°C (Lit. 192-195°C) ; 1H NMR (DMSO-.d5) δ : 8.15 (s, IH, H-2), 8.06 (s, IH, H-8) , 7.22 (bs, 2H, NH2), 5.06 (bs, IH, OH), 4.06 (m, 3H, CH2N and CHO), 1.12 (d, J = 5.7 Hz, 3H, CH3). 13C NMR (OMSO-d6) δ: 155.87, 152.21, 149.67, 141.44, 118.50, 64.57, 50.07, 20.80. MS (GT, FAB+): 136 (B+1H) \\ 194 (M+1H)+, 216 (MH-Na)+, 232 (M+K) +, 387 (2MH-IH)+.
81%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide at 100 - 120℃; Inert atmosphere
Stage #2: at 120℃; for 8 h;
The Buchi reactor (10 L) was preheated to 150 °C and traces of moisture were blown away with the nitrogen stream. The reactor was filled with argon and cooled down to ~ 70 °C, dry DMF (4 L, ~ 20 ppm of H2O, distilled from P2O5) was added and stirring was switched on (200 rev/min) with heating at 100 °C. When the desired temperature was reached, adenine (A, 150 g, 1 mol) and K2CO3 (72.5 g, 0.525 mol) were added. The reaction temperature was increased to 120 °C. The coarse suspension changed into fine suspension of the potassium salt of adenine and CO2 was being released at the same time. When temperature of 120 °C was reached, carbonate (R)-C (133 g, 1.3 mol) was immediately and quickly added. The reaction mixture was stirred at 120 °C and continuously monitored by TLC. The full conversion was observed at ~ 8 h. The reaction mixture was then cooled to RT and precipitated solid was filtered off, the reactor was rinsed with EtOH, and the solid washed quickly with EtOH (2 x 100 mL). The filtrate was concentrated in vacuo at 60 °C, so that ~ 200 mL of DMF are left in the flask, i.e. ~ 400 mL of solvents were removed. The product usually started to crystallize during the concentration/evaporation process. EtOH (400 mL) was added to the residue and this mixture was sonicated at 70 °C for 2 h to convert the formylated by-product to the desired product 1 and to afford nicely crystallized product 1. After cooling in an ice bath, the product was filtered off, washed (2 x 50 mL iced EtOH), and dried at 60°C for 4 days (under vacuum with P2O5) to give 149 g (72percent) of 1 (98percent purity, HPLC). Repeated experiments afforded up to 81 percent yields of the product 1
72%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide at 100 - 120℃; Inert atmosphere
Stage #2: at 120℃; for 8 h;
The Buchi reactor (10 L) was preheated to 150 °C and traces of moisture were blown away with the nitrogen stream. The reactor was filled with argon and cooled down to ~ 70 °C, dry DMF (4 L, ~ 20 ppm of H2O, distilled from P2O5) was added and stirring was switched on (200 rev/min) with heating at 100 °C. When the desired temperature was reached, adenine (A, 150 g, 1 mol) and K2CO3 (72.5 g, 0.525 mol) were added. The reaction temperature was increased to 120 °C. The coarse suspension changed into fine suspension of the potassium salt of adenine and CO2 was being released at the same time. When temperature of 120 °C was reached, carbonate (R)-C (133 g, 1.3 mol) was immediately and quickly added. The reaction mixture was stirred at 120 °C and continuously monitored by TLC. The full conversion was observed at ~ 8 h. The reaction mixture was then cooled to RT and precipitated solid was filtered off, the reactor was rinsed with EtOH, and the solid washed quickly with EtOH (2 x 100 mL). The filtrate was concentrated in vacuo at 60 °C, so that ~ 200 mL of DMF are left in the flask, i.e. ~ 400 mL of solvents were removed. The product usually started to crystallize during the concentration/evaporation process. EtOH (400 mL) was added to the residue and this mixture was sonicated at 70 °C for 2 h to convert the formylated by-product to the desired product 1 and to afford nicely crystallized product 1. After cooling in an ice bath, the product was filtered off, washed (2 x 50 mL iced EtOH), and dried at 60°C for 4 days (under vacuum with P2O5) to give 149 g (72percent) of 1 (98percent purity, HPLC). Repeated experiments afforded up to 81 percent yields of the product 1
71.8%
Stage #1: With sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.333333 h;
Stage #2: at 120℃; for 24.5 h;
40 g (0.296 mol) of adenine To 200 ml of dimethylformamide (DMF)And dissolved 0.94 g (0.0235 mol, 0.08 equiv.) Of sodium hydroxide (NaOH)Followed by stirring at room temperature for 20 minutes39.2 g (0.390 mol, 1.32 Equiv.) Of (R) -propylene carbonate ((R) -propylene carbonate) was added and stirred for 30 minutes.The reaction temperature was 120 [And heated and condensed for 24 hours.Thereafter, the reaction was checked by TLC and HPLC. After the reaction was almost completed (90percent or more), the reaction temperature was cooled to 70 ° C and 240 ml of isopropyl alcohol (IPA) was added to crystallize. Thereafter, the solution was continuously stirred and cooled. The crystals were filtered at 10 ° C, washed with IPA, and dried in a vacuum dryer at 70 ° C to obtain 41 g of HPA (yield: 71.8percent).
71.8%
Stage #1: With sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.333333 h;
Stage #2: at 120℃; for 24.5 h;
40 g (0.296 mol) of 6 adenine was dissolved in 200 ml of 7 dimethylformamide (DMF), and 0.94 (0.0235 mol, 0.08 eq.) of 8 sodium hydroxide (NaOH) was added. After 20-min agitation at the room temperature, 39.2 g (0.390 mol, 1.32 eq.) of 9 (R)-propylene carbonate was added and the resultant solution was stirred for 30 minutes. The reaction temperature was elevated to 120° C., and a thermal condensation reaction was activated for 24 hours. Subsequently, the reaction status was examined through TLC and HPLC. After the completion of the reaction (90percent or above), the reaction temperature was reduced to 70° C. and 240 ml of isopropyl alcohol (IPA) was added to active crystallization. Under continuous agitation and cooling, crystals were collected through filtration at 10° C., washed with IPA and then dried out at 70° C. in a low-pressure dryer to obtain 41 g of 5 HPA (yield 71.8percent).
65%
Stage #1: With potassium hydroxide In N,N-dimethyl-formamide at 25 - 30℃; for 0.166667 h;
Stage #2: at 25 - 120℃;
Stage #3: With methanol In N,N-dimethyl-formamide; isopropyl alcohol at 55 - 70℃; for 0.166667 h;
Example 2 (Stage 1 using KOH)Adenine 4 (40 g, 296 mmol, 1.0 eq) and potassium hydroxide (1.66 g, 29.6 mmol, 0.1 eq) were mixed with DMF (190 ml) at 25-30 °C and the mixture was stirred for 10 mm at 25-30 °C. (R)-propylene carbonate 5 (33.6 ml, 39.9 g, 391 mmol, 1.32 eq) was added drop-wise to the reaction mass over10-15 mm at 25-30 °C. The mixture was heated to 120 °C and held at that temperature for 48 h. A clear solution resulted, and the reaction mixture was cooled to 70 °C. A mixture of methanol (120 ml) and iso-propanol (120 ml) was added drop-wise to the reaction mixture over 10 mm, during which time the reaction mixture was allowed to cool to 55 °C, and precipitation of produt was observed. The reaction mixturewas cooled to 5 °C and held at this temperature for I h. The product was isolated by filtration and the cake was washed with a chilled mixture of methanol (10 ml) and isopropanol (10 ml). The resulting solid was dried under vacuum at 70-75 °C, affording HPA 6 as an off-white solid (37 g, 65percent).

Reference: [1] Patent: CN103848869, 2016, B, . Location in patent: Paragraph 0053; 0054
[2] Patent: CN103848868, 2017, B, . Location in patent: Paragraph 0055; 0058; 0059
[3] Journal of Medicinal Chemistry, 2006, vol. 49, # 26, p. 7799 - 7806
[4] Patent: WO2008/56264, 2008, A2, . Location in patent: Page/Page column 69-70; 75; 81
[5] Patent: WO2015/51874, 2015, A1, . Location in patent: Page/Page column 6; 20; 21
[6] Patent: EP2860185, 2015, A1, . Location in patent: Paragraph 0018; 0027
[7] Patent: KR2016/135112, 2016, A, . Location in patent: Paragraph 0070; 0071; 0072; 0073
[8] Patent: US2017/354668, 2017, A1, . Location in patent: Paragraph 0101; 0102
[9] Organic Process Research and Development, 2010, vol. 14, # 5, p. 1194 - 1201
[10] Patent: WO2014/33688, 2014, A1, . Location in patent: Page/Page column 23
[11] Organic Process Research and Development, 2016, vol. 20, # 4, p. 742 - 750
[12] Tetrahedron Letters, 1998, vol. 39, # 14, p. 1853 - 1856
[13] Patent: EP1243590, 2002, A2, . Location in patent: Page 9
[14] Patent: US2010/216822, 2010, A1, . Location in patent: Page/Page column 14
[15] Patent: CN102977146, 2016, B, . Location in patent: Paragraph 0016; 0024-0025
[16] Patent: CN105859781, 2016, A, . Location in patent: Paragraph 0013-0014
[17] Patent: CN104262397, 2016, B, . Location in patent: Paragraph 0029; 0030
[18] Patent: CN106349289, 2017, A, . Location in patent: Paragraph 0026; 0027; 0028; 0031; 0032
[19] Patent: CN108358968, 2018, A, . Location in patent: Paragraph 0073; 0087; 0091; 0134; 0138; 0142; 0146; 0150
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Reference: [1] Patent: JP2015/164934, 2015, A, . Location in patent: Paragraph 0166; 0167; 0175
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YieldReaction ConditionsOperation in experiment
92.9 %Chromat.
Stage #1: With sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 0.333333 h;
Stage #2: at 120 - 130℃; for 16 h;
Step 1: The crude R-9- (2-hydroxypropyl) adenine was obtained100 g of adenine (0.74 mol) and 2.35 g (0.058 mol) of sodium hydroxide were added to 500 mlAnd stirred at room temperature for 20 minutes. 96.5 g (0.946 mol) of R-propylene carbonate was added and the temperature was raised to 120-130 ° C to maintain the temperature of the reaction mixtureShould be 16h;After the completion of the reaction by HPLC, the solution of R-9- (2-hydroxypropyl) adenine which had been reacted was distilled off under reduced pressure for 70 ~80percent of the DMF solvent, adding 300ml toluene, stirring evenly, 0 degrees heat 2h, filtration, drying, in the R-9- (2-hydroxypropyl)The crude product of adenine was 136 g, the crude yield was 95.7percent, the purity was 90.8percent, and the isomer was 8.0percent.Step two: packed column, pretreatmentA 150 g of PRP-6A resin was weighed, poured into a glass column, rinsed three times with ethanol, and the column was compactedNo bubbles, the resin height of 28cm, the cylinder uniform, and then rinse with ethyl acetate 3 times, and finally replaced with ethanol, ethyl acetateTo the test without ethyl acetate so far, the column installed backup.Step 3: LoadingThe crude R-9- (2-hydroxypropyl) adenine 6g dissolved in a small amount of water 20ml, into the PRP-6A resin chromatography column,To the sample solution completely adsorbed to the resin column for the sample is completed.Step 4: Elution80percent ethanol as the eluant, pour into the resin column, with air pump pressure elution, flow controlAt 15 ml / min, the eluent was received in 100 ml portions of the receiver bottle, and the content of the product in each bottle was detected by HPLC.Step 5: ConcentrationThe R-9- (2-hydroxypropyl) adenine and the isomer were collected together under vacuum conditions with a purity of more than 99percentConcentrated to dry, distilled ethanol water recovery applied to get more than 99percent purity of R-9- (2-hydroxypropyl) adenine white crystalline powderAnd 4.7 g of isomer having a purity of more than 99percent, and the chromatographic separation yield was 92.9percent of the product and 97.9percent of the isomer.Step 6: Wash the columnRinse the column with 90percent ethanol in water until no liquid is detected. This indicates that the PRP-6A resin column has been flushedClean, you can continue to use the next time.Step 6: Repeat steps 3 through 6 to cycle through the column 6 timesThe results are shown in Table 1 below:Note: In Table 1 above, the chromatographic separation results were obtained in the longitudinal direction for six times. The yield was chromatographic yield,HPLC area integral purity.
Reference: [1] Patent: CN104892613, 2016, B, . Location in patent: Paragraph 0023; 0024; 0025; 0026; 0027; 0028; 0029-0034
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Reference: [1] Journal of Heterocyclic Chemistry, 2016, vol. 53, # 2, p. 579 - 582
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YieldReaction ConditionsOperation in experiment
90% at 105 - 110℃; for 8 h; Large scale R - Preparation of propylene carbonate,R-1,2-propanediol was added to a glass-lined reactor(38.05 kg, 500Mol),Diethyl carbonate(70.88 kg, 600 mol) and (3.4 kg, 50 mol) of sodium ethoxide,Heated to 105-110 ° C,Reaction for 8 hours,The reaction is terminated,The unreacted diethyl carbonate was distilled off under reduced pressure,Cooled to room temperature,Filter insoluble matter,The filtrate was evaporated to remove the solvent of product R - propylene carbonate 34.24 kg,Purity ≥ 99percentThe yield was 90percent.
81.2% With sodium methylate In ethanol at 80℃; Example 1
Preparation of (R)-4-methyl-1,3-dioxolan-2-one
To the mixture of diethyl carbonate (380 ml, 15.1 mol) and 200 g of (R)-1,2-propanediol was added 40 ml of denatured ethanol (the solution of 9 g sodium methoxide dissolved in 50 ml of anhydrous ethanol), the resulting solution was heated to 80° C., then ethanol was distilled off slowly.
The reaction process was monitored by TLC, after TLC showed that only trace amount of (R)-1,2-propanediol remained or (R)-1,2-propanediol was undetectable, ethanol was distilled under vacuum by water pump at 120° C. until no ethanol dropped out.
The residue was distilled under vacuum to give the title compound as a colorless transparent liquid (111 g, 81.2percent yield, purity 97percent by GC)
44.5 g With sodium ethanolate In ethanol at 80℃; The 1000 ml hydrogenation vessel was evacuated and then passed through nitrogen,Then add 500ml ethanol, 2g5percent Pd / C, 2.5g caustic soda, cool to -10 ,Slowly add 50g of S-glycidol,Then, hydrogen gas (about 2 atmospheres) was passed for 4 hours,To no longer consume hydrogen so far, filtered and concentrated to give 48 g of a colorless oil.
Reference: [1] Patent: CN105859781, 2016, A, . Location in patent: Paragraph 0011-0012
[2] Patent: US2010/216822, 2010, A1, . Location in patent: Page/Page column 13
[3] Tetrahedron Letters, 1998, vol. 39, # 14, p. 1853 - 1856
[4] Patent: EP1243590, 2002, A2, . Location in patent: Page 9
[5] Patent: CN102977146, 2016, B, . Location in patent: Paragraph 0016; 0021; 0023
[6] Patent: CN108358968, 2018, A, . Location in patent: Paragraph 0073; 0087-0089; 0134-0136; 0142-0144; 0150-0152
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  • [ 16606-55-6 ]
YieldReaction ConditionsOperation in experiment
99% at 120℃; for 4 h; Autoclave General procedure: For a typical reaction of CO2with epoxides, ZnBr2(11.3 mg,0.05 mmol), [BMIM]Br (65 mg, 0.3 mmol) and epoxides (PO: 20 ml,0.286 mol; or ECH: 23.61 g, 0.255 mmol) were charged into a100 ml stainless steel autoclave equipped with a magnetic stirrerin sequence. The 3.0 MPa of CO2was filled into the reaction ves-sel which was then heated to 120C for 4 h. Once the reaction iscompleted, the vessel was cooled to room temperature and thegas was released slowly. Then the liquid phase was analyzed byHP7890A/5975C GC–MS. The unreacted substrate was then dis-tilled out from the mixture, and the product was obtained. Theenantiomeric purity of the mixture was analyzed by HP7890A GCequipped with a chiral DEX120 chromatography column.
Reference: [1] Journal of Organic Chemistry, 2008, vol. 73, # 20, p. 8039 - 8044
[2] Journal of Molecular Catalysis A: Chemical, 2014, vol. 385, p. 133 - 140
[3] ChemSusChem, 2017, vol. 10, # 15, p. 3025 - 3029
[4] Green Chemistry, 2017, vol. 19, # 16, p. 3769 - 3779
[5] Journal of the American Chemical Society, 2014, vol. 136, # 43, p. 15270 - 15279
[6] Chemical Communications, 2004, # 14, p. 1622 - 1623
[7] Journal of the American Chemical Society, 2001, vol. 123, # 46, p. 11498 - 11499
[8] Advanced Synthesis and Catalysis, 2009, vol. 351, # 9, p. 1325 - 1332
[9] Green Chemistry, 2011, vol. 13, # 3, p. 644 - 650
[10] Inorganic Chemistry, 2012, vol. 51, # 21, p. 12041 - 12052,12
[11] Journal of Organic Chemistry, 2014, vol. 79, # 20, p. 9771 - 9777
[12] ACS Catalysis, 2015, vol. 5, # 11, p. 6773 - 6779
  • 12
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  • [ 51260-39-0 ]
  • [ 16606-55-6 ]
YieldReaction ConditionsOperation in experiment
34.2% With C126H91CoN12O10; tetrabutyl-ammonium chloride In dichloromethane at 25℃; for 96 h; Autoclave General procedure: All reactions were conducted in a 100 mL stainless steel autoclave equipped with a magnetic stir bar, and submerged in anoil bath. The required catalyst, tetrabutylammonium chloride (TBAC) as the co‐catalyst, epoxide, and CH2Cl2 were added tothe reactor in turn. The reactor was then charged with CO2 and vented three times, and finally pressurized with CO2 to 1.0 MPa. The contents were then stirred at room temperature for an established period that depended on the selected substrate and catalyst, after which the reactor was carefully discharged to atmospheric pressure. The yield of cyclic carbonate was determinedby the subtraction method or by comparison betweenthe integral areas obtained by 1H NMR spectroscopy for thecyclic carbonate and epoxide.
31.6% With C126H91CoN12O10; tetrabutyl-ammonium chloride In dichloromethane at 25℃; for 96 h; Autoclave General procedure: All reactions were conducted in a 100 mL stainless steel autoclave equipped with a magnetic stir bar, and submerged in anoil bath. The required catalyst, tetrabutylammonium chloride (TBAC) as the co‐catalyst, epoxide, and CH2Cl2 were added tothe reactor in turn. The reactor was then charged with CO2 and vented three times, and finally pressurized with CO2 to 1.0 MPa. The contents were then stirred at room temperature for an established period that depended on the selected substrate and catalyst, after which the reactor was carefully discharged to atmospheric pressure. The yield of cyclic carbonate was determinedby the subtraction method or by comparison betweenthe integral areas obtained by 1H NMR spectroscopy for thecyclic carbonate and epoxide.
38.8 % ee at 25℃; for 25 h; Autoclave General procedure: A solution of freshly prepared SalenCo(III)Y (0.1 mmol) andepoxide (100 mmol) was introduced into a 100 mL stainless-steelautoclave, which was purged three times and charged with CO2to 1.2 MPa. The reaction mixture was stirred at room temperature.When the pressure of reactor was fall down to a presetting value, itwas then vented carefully. After removing the excess epoxide, theresidue was weighed to measure the conversion of epoxide, chiralcyclic carbonate (R = Me, Et, CH2Cl) was distilled under vacuum as asa colorless liquid or it (R = Ph, PhOCH2) was obtained by columnchromatography through a short silica–gel column to yield whitesolid product (ethyl acetate/petroleum ether = 5:1).
Reference: [1] Dalton Transactions, 2013, vol. 42, # 27, p. 9930 - 9937
[2] Chinese Journal of Catalysis, 2018, vol. 39, # 5, p. 997 - 1003
[3] Chinese Journal of Catalysis, 2018, vol. 39, # 5, p. 997 - 1003
[4] Journal of the American Chemical Society, 2004, vol. 126, # 12, p. 3732 - 3733
[5] Chemical Communications, 2004, # 14, p. 1622 - 1623
[6] Tetrahedron Letters, 2007, vol. 48, # 2, p. 297 - 300
[7] Tetrahedron Letters, 2008, vol. 49, # 46, p. 6589 - 6592
[8] Advanced Synthesis and Catalysis, 2009, vol. 351, # 9, p. 1325 - 1332
[9] Advanced Synthesis and Catalysis, 2009, vol. 351, # 9, p. 1325 - 1332
[10] Green Chemistry, 2009, vol. 11, # 7, p. 935 - 938
[11] Green Chemistry, 2009, vol. 11, # 7, p. 935 - 938
[12] Science China Chemistry, 2011, vol. 54, # 7, p. 1044 - 1050
[13] Science China Chemistry, 2011, vol. 54, # 7, p. 1044 - 1050
[14] Catalysis Science and Technology, 2013, vol. 3, # 10, p. 2661 - 2667
[15] Journal of Molecular Catalysis A: Chemical, 2016, vol. 411, p. 34 - 39
[16] RSC Advances, 2016, vol. 6, # 4, p. 3243 - 3249
[17] Chemical Communications, 2017, vol. 53, # 79, p. 10930 - 10933
[18] Chemical Communications, 2017, vol. 53, # 79, p. 10930 - 10933
[19] Chinese Journal of Catalysis, 2018, vol. 39, # 5, p. 997 - 1003
  • 13
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YieldReaction ConditionsOperation in experiment
66.7 % ee at 25℃; for 8 h; Autoclave General procedure: Catalyst of (S,R,R,S)-ZSS-2b (631 mg, 0.1 mmol), cocatalyst of tetrabutylammonium fluoride (TBAF, 0.0522 g, 0.2 mmol), and racemic propylene oxide (PO, 7 mL, 100 mmol) were introduced into a 100-mL stainless steel autoclave to form a brown solution. The reactor was purged thrice with carbon dioxide, and charged it to 0.8 MPa. Then, the asymmetric catalytic reaction took place at room temperature. After some time, the pressure in the reactor decreased to an expected value, and it was vented to terminate the reaction. After removing the unreacted epoxide, chiral cyclic carbonate (R=Me, Et, CH2Cl), weighed to calculate the yield of cyclic carbonate, was distilled under vacuum as a colorless liquid or it (R=Ph, PhOCH2) was obtained by column chromatography through a short silica gel column (ethyl acetate:petroleum ether = 5:1).
Reference: [1] Tetrahedron Asymmetry, 2008, vol. 19, # 16, p. 1947 - 1953
[2] Catalysis Communications, 2016, vol. 81, p. 50 - 53
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YieldReaction ConditionsOperation in experiment
66.8 % ee at 0℃; for 8 h; Autoclave General procedure: Catalyst of (S,R,R,S)-ZSS-2b (631 mg, 0.1 mmol), cocatalyst of tetrabutylammonium fluoride (TBAF, 0.0522 g, 0.2 mmol), and racemic propylene oxide (PO, 7 mL, 100 mmol) were introduced into a 100-mL stainless steel autoclave to form a brown solution. The reactor was purged thrice with carbon dioxide, and charged it to 0.8 MPa. Then, the asymmetric catalytic reaction took place at room temperature. After some time, the pressure in the reactor decreased to an expected value, and it was vented to terminate the reaction. After removing the unreacted epoxide, chiral cyclic carbonate (R=Me, Et, CH2Cl), weighed to calculate the yield of cyclic carbonate, was distilled under vacuum as a colorless liquid or it (R=Ph, PhOCH2) was obtained by column chromatography through a short silica gel column (ethyl acetate:petroleum ether = 5:1).
Reference: [1] Catalysis Communications, 2016, vol. 81, p. 50 - 53
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Reference: [1] Synthesis, 2009, # 8, p. 1403 - 1404
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  • [ 1015235-29-6 ]
  • [ 1015235-28-5 ]
  • [ 16606-55-6 ]
YieldReaction ConditionsOperation in experiment
99.67 % ee With sodium hydroxide In water at 20℃; for 25.5 h; Aqueous phosphate buffer; D-glucose Example 1 Biocatalytic reduction of 0- (methoxycarbonyl) -hydroxyacetone, 2a :4aIn a Titrino reaction vessel, the whole-cell catalyst of type E. coli DSM14459, containing an (R) -alcohol dehydrogenase from L. kefir and a glucose dehydrogenase from T. acidophilum (for production of the biocatalyst, see WO2005121350) , at a cell concentration of 55 g moist biomass / L, D-glucose (1.5 equivalents relative to the molar amount of ketone used) and 25 mmol 0-(methyloxycarbonyl) -hydroxyacetone, 2a, (corresponding to a substrate concentration of 0.5M) are added to 30 mL of an aqueous phosphate buffer (0.026 M; adjusted to pH 7.0) and the volume is topped up to 50 mL with water. The reaction mixture is stirred for a reaction time of 25.5 hours at room temperature, maintaining constant pH at -6.5 by adding sodium hydroxide solution (5M NaOH). After a reaction time of 25.5 hours, conversion of >95percent is determined (according to the consumption of sodium hydroxide solution and GC chromatography) . Processing is carried out by lowering the pH value to <3 with concentrated hydrochloric acid and addition of 3.75 g of the filter aid Celite Hyflo <n="25"/>Supercel to the reaction mixture, followed by filtration with application of vacuum. The filter cake is washed 4 times with 50 mL MTBE and the aqueous phase is extracted correspondingly with the three organic MTBE fractions obtained. The solvent is removed from the combined organic phases after drying over magnesium sulphate, yielding as raw product the optically active alcohol 3a at a yield of 50percent (of which 12.7 mol.percent is rearranged to give the regioisomeric alcohol 4a and 63.6 mol.percent has already been cyclized to the desired (R) -propylene carbonate 1) . The enantioselectivity of the reaction is 99.67percent ee .
Reference: [1] Patent: WO2008/34685, 2008, A1, . Location in patent: Page/Page column 22-23
  • 17
  • [ 105235-63-0 ]
  • [ 1015235-30-9 ]
  • [ 1015235-31-0 ]
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YieldReaction ConditionsOperation in experiment
99.34 % ee With sodium hydroxide In water at 20℃; for 25.5 h; Aqueous phosphate buffer; D-glucose Example 2_Biocatalytic reduction of 0- (ethoxycarbonyl) - hydroxyacetone, 2b:4bIn a Titrino reaction vessel, the whole-cell catalyst of type E. coli DSM14459, containing an (R) -alcohol dehydrogenase from L. kefir and a glucose dehydrogenase from T. acidophilum (for production of the biocatalyst, see WO2005121350) , at a cell concentration of 51 g moist biomass / L, D-glucose (1.5 equivalents relative to the molar amount of ketone used) and 25 mmol 0- (ethyloxycarbonyl) -hydroxyacetone, 2b, (corresponding to a substrate concentration of 0.5M) are added to 30 mL of an aqueous phosphate buffer (0.026 M; adjusted to pH 7.0) and the volume is topped up to 50 mL with water. The reaction mixture is stirred for a reaction time of 25.5 hours at room temperature, maintaining constant pH at -6.5 by adding sodium hydroxide solution (5M NaOH) . After a reaction time of 25.5 hours, conversion of >95percent is determined (according to the consumption of sodium hydroxide solution and GC chromatography) . Processing is carried out by lowering the pH value to <3 with concentrated hydrochloric acid and addition of 3.75 g of the filter aid Celite Hyflo Supercel to the reaction mixture, followed by filtration with application of vacuum. The filter cake is washed 4 times with 50 mL MTBE and the aqueous phase <n="27"/>is extracted correspondingly with the three organicMTBE fractions obtained. The solvent is removed from the combined organic phases after drying over magnesium sulphate, yielding as raw product the optically active alcohol 3b at a yield of 71percent (of which 37.3 mol.percent is rearranged to give the regioisomeric alcohol 4a and18.6 mol.percent has already been cyclized to the desired(R) -propylene carbonate 1) . The enantioselectivity of the reaction is 99.34percent ee
Reference: [1] Patent: WO2008/34685, 2008, A1, . Location in patent: Page/Page column 24-25
  • 18
  • [ 1015235-30-9 ]
  • [ 1015235-31-0 ]
  • [ 16606-55-6 ]
YieldReaction ConditionsOperation in experiment
99.18 % ee at 60℃; for 6 h; Example 4_Synthesis of (R) -propylene carbonate 1 by cyclization of the raw product from Example 2:HO.XH-,4b0.525 g of the optically active alcohol 3b obtained as raw product according to example 2 (which has partially been rearranged to give the regioisomeric alcohol 4b or has already been cyclized to the desired (R) -propylene carbonate according to the proportions stated in mol.percent in example 2) is absorbed in 10 mL ethyl acetate, and p-toluenesulphonic acid (96 mg) is added. The reaction mixture is heated for 6 hours at a reaction temperature of 600C. The desired (R) -propylene carbonate 1 is obtained in a proportion of -80percent (relative to the molar quantity of substrate used from example 2) and with an enantioselectivity of 99.18percent ee
Reference: [1] Patent: WO2008/34685, 2008, A1, . Location in patent: Page/Page column 28
  • 19
  • [ 57-55-6 ]
  • [ 584-08-7 ]
  • [ 16606-55-6 ]
Reference: [1] Patent: US6054596, 2000, A,
  • 20
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  • [ 51260-39-0 ]
  • [ 15448-47-2 ]
  • [ 16088-62-3 ]
  • [ 16606-55-6 ]
Reference: [1] Organic Letters, 2006, vol. 8, # 20, p. 4401 - 4404
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Reference: [1] Organic Letters, 2006, vol. 8, # 20, p. 4401 - 4404
  • 22
  • [ 4254-14-2 ]
  • [ 616-38-6 ]
  • [ 16606-55-6 ]
Reference: [1] European Journal of Organic Chemistry, 2018, vol. 2018, # 23, p. 2931 - 2938
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