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Product Details of [ 611-71-2 ]

CAS No. :611-71-2 MDL No. :MFCD00064251
Formula : C8H8O3 Boiling Point : -
Linear Structure Formula :- InChI Key :IWYDHOAUDWTVEP-SSDOTTSWSA-N
M.W : 152.15 Pubchem ID :11914
Synonyms :
R-(-)-Mandelic Acid;D-(−)-Mandelic Acid;D-α-Hydroxyphenylacetic acid;D-Mandelic acid;(R)-(-)-Mandelic acid
Chemical Name :(R)-2-Hydroxy-2-phenylacetic acid

Calculated chemistry of [ 611-71-2 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.12
Num. rotatable bonds : 2
Num. H-bond acceptors : 3.0
Num. H-bond donors : 2.0
Molar Refractivity : 39.15
TPSA : 57.53 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.79 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.92
Log Po/w (XLOGP3) : 0.62
Log Po/w (WLOGP) : 0.48
Log Po/w (MLOGP) : 0.78
Log Po/w (SILICOS-IT) : 0.76
Consensus Log Po/w : 0.71

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -1.45
Solubility : 5.45 mg/ml ; 0.0358 mol/l
Class : Very soluble
Log S (Ali) : -1.4
Solubility : 6.02 mg/ml ; 0.0396 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.23
Solubility : 9.02 mg/ml ; 0.0593 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.59

Safety of [ 611-71-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P264-P271-P280-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 611-71-2 ]

* 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.

  • Upstream synthesis route of [ 611-71-2 ]
  • Downstream synthetic route of [ 611-71-2 ]

[ 611-71-2 ] Synthesis Path-Upstream   1~30

  • 1
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  • [ 276252-73-4 ]
YieldReaction ConditionsOperation in experiment
90%
Stage #1: With sodium hydroxide In water at 50 - 120℃; for 1 - 4 h;
Stage #2: With hydrogenchloride In water
The D-mandelate (R,S,S salt 2, 266.5 g, 1 mol) was dissolved in 20percent sodium hydroxide solution (400 ml) and stirred at 50° C. for one hour. This resulted in a clear solution. The bath temperature was increased to 120° C. and the released S,S-DiMeMo was distilled off in an azeotrope with water (at 100° C.) by means of a distillation apparatus. After approx. 300 ml of condensate had distilled over, the distillation receiver was cooled to room temperature and acidified with 10percent HCl. The precipitated mandelic acid was filtered off with suction and dried under reduced pressure. An analysis of the optical purity showed that the D-mandelic acid had racemized fully.The condensate which had distilled over was saturated by adding solid NaOH; an organic phase separated out and was diluted with MTBE (200 ml). Extraction was effected with MTBE (2.x.100 ml), and the extracts were combined, dried over Na2SO4 and concentrated by rotary evaporation. 101 g of crude product were obtained and were fractionated in a water-jet pump vacuum. The pure S,S-DiMeMo distilled over at 37-39° C./14 mm. 88 g (18percent based on trans-DiMeMo racemate used) of S,S-DiMeMo were obtained as clear oil.Rotation [α]D=-6.15°(pure, d=0.94 g*cm-3). According to GC analysis, the optical purity of the isolated S,S-DiMeMo was 97.9percent ee.
Reference: [1] Patent: US2009/12289, 2009, A1, . Location in patent: Page/Page column 2
  • 2
  • [ 1257267-06-3 ]
  • [ 3426-71-9 ]
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Reference: [1] Biochemistry, 2010, vol. 49, # 49, p. 10496 - 10506
  • 3
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  • [ 54852-85-6 ]
  • [ 1081548-91-5 ]
  • [ 550-58-3 ]
Reference: [1] Organic Letters, 2013, vol. 15, # 21, p. 5594 - 5597
  • 4
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  • [ 4870-65-9 ]
YieldReaction ConditionsOperation in experiment
78% for 3 h; Reflux DL-Mandelic acid 1b (30.4 g; 0.20 mol) was gradually introduced into a solution of 40percent HBr (56 mL) and concentrated H2SO4 (22 mL). The mixture was refluxed for 3 h, cooled and poured onto ice (150 g). The solution was then extracted twice with diethyl ether (2.x.75 mL), dried over MgSO4 and concentrated on a rotary evaporator. The remaining brown solution was distilled under reduced pressure. The crude product was crystallised from hexane, yielding pure α-bromophenylacetic acid 2b as light-yellow crystals (33.5 g, 78percent yield), mp 83-84 °C (lit.:12 mp 68-69 °C), Rf (benzene/ethyl acetate/AcOH, 1:3:1 v/v/v) 0.70.
75% With sulfuric acid; hydrogen bromide In water for 3 h; Reflux dl-Mandelic acid 1 (30.4 g; 0.20 mol) was gradually introduced into a solution of 40percent HBr (56 mL) and concentrated H2SO4 (22 mL). The mixture was kept under reflux for 3 h, cooled and poured onto ice (150 g). The solution was then extracted twice with diethyl ether (2.x.75 mL), dried over MgSO4 and concentrated on the rotary evaporator. The remaining brown solution was distilled under reduced pressure. The crude product was crystallised from hexane, yielding pure α-bromophenylacetic acid 2 as light-yellow crystals; yield: 75percent, mp 83-84 °C (lit.:refPreviewPlaceHolder34 mp 82-84 °C), Rf (benzene/ethyl acetate, 1:3 v/v) 0.70.
Reference: [1] Tetrahedron, 2012, vol. 68, # 18, p. 3616 - 3625
[2] Tetrahedron, 2011, vol. 67, # 44, p. 8502 - 8508
[3] Journal of the Chemical Society, 1957, p. 4789,4792
[4] Journal fuer Praktische Chemie (Leipzig), 1917, vol. <2> 96, p. 286[5] Journal fuer Praktische Chemie (Leipzig), 1919, vol. <2> 99, p. 205
[6] Zeitschrift fuer Chemie, 1868, p. 142
[7] Zeitschrift fuer Chemie, 1868, p. 142
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  • [ 100-52-7 ]
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  • [ 65-85-0 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1987, p. 945 - 951
  • 6
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Reference: [1] Justus Liebigs Annalen der Chemie, 1890, vol. 258, p. 76,86
[2] Zeitschrift fuer Chemie, 1868, p. 142
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  • [ 17119-15-2 ]
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  • [ 65-85-0 ]
Reference: [1] Journal of the American Chemical Society, 1982, vol. 104, # 5, p. 1185 - 1189
  • 8
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  • [ 21210-43-5 ]
Reference: [1] Tetrahedron Asymmetry, 2005, vol. 16, # 12, p. 2113 - 2117
[2] Tetrahedron Asymmetry, 2005, vol. 16, # 12, p. 2113 - 2117
[3] Biochemische Zeitschrift, 1927, vol. 181, p. 51
[4] Crystal Growth and Design, 2014, vol. 14, # 7, p. 3549 - 3556
[5] Crystal Growth and Design, 2014, vol. 14, # 7, p. 3549 - 3556
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Reference: [1] Beilstein Journal of Organic Chemistry, 2010, vol. 6, p. 1043 - 1055
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  • [ 947-94-4 ]
Reference: [1] European Journal of Organic Chemistry, 2017, vol. 2017, # 16, p. 2290 - 2304
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Reference: [1] Advanced Synthesis and Catalysis, 2011, vol. 353, # 8, p. 1234 - 1240
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Reference: [1] Tetrahedron Asymmetry, 2002, vol. 13, # 12, p. 1337 - 1345
[2] Tetrahedron Asymmetry, 2003, vol. 14, # 23, p. 3679 - 3687
[3] Advanced Synthesis and Catalysis, 2007, vol. 349, # 7, p. 1119 - 1127
  • 13
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Reference: [1] Canadian Journal of Chemistry, 1990, vol. 68, p. 314 - 316
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  • [ 7322-88-5 ]
YieldReaction ConditionsOperation in experiment
49% With immobilized lipase B from Candida antarctica; ammonia In di-isopropyl ether at 25℃; for 12 h; Resolution of racemate; Enzymatic reaction General procedure: A 25 ml round-bottom flask was charged with Racemic α-hydroxyl acid ester of 0.5 mmol, 10 mLisopropyl ether and immobilized CALB (Novozym 435), the flask was sealed and anhydrous ammonia was added through the solution. The resulting mixture was stirred at 35 °C for a certain time. Samples were taken at 1 h intervals, each time 20 µl of solution were used for analyzing. When the reaction was complete, the solution was filtered through a pad of cotton and the solvent was removed in vacuum. The resulting residues were purified by chromatography on silica gel with petroleum ether–ethyl acetate (1:1 –1:5) to afford the corresponding α-hydroxyl acid, yields and ee values of the desired product were summarized in Table 2.
Reference: [1] Tetrahedron Letters, 2016, vol. 57, # 48, p. 5312 - 5314
  • 15
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YieldReaction ConditionsOperation in experiment
99 % ee With lipase LC2-8 from P. stutzeri LC2-8 In di-isopropyl ether at 30℃; Resolution of racemate; Enzymatic reaction The resolution of (R,S)-mandelic acid was carried out in isopropyl ether containing 300 mM vinyl acetate and 30 mM mandelic acid. The reaction was carried out with shaking at 180 rpm, and was catalyzed by 10 mg/mL (30 U/mL) lipase LC2-8 powder at 30°C. A control reaction was done by performing the above procedure in the absence of enzyme.
Reference: [1] Journal fuer Praktische Chemie/Chemiker-Zeitung, 1992, vol. 334, # 6, p. 526 - 528
[2] Journal of Molecular Catalysis B: Enzymatic, 2013, vol. 85-86, p. 105 - 110
[3] Journal of Molecular Catalysis B: Enzymatic, 2014, vol. 99, p. 108 - 113
  • 16
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Reference: [1] Tetrahedron Asymmetry, 1999, vol. 10, # 21, p. 4079 - 4081
  • 17
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Reference: [1] Tetrahedron Letters, 2016, vol. 57, # 48, p. 5312 - 5314
  • 18
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  • [ 75-36-5 ]
  • [ 51019-43-3 ]
Reference: [1] Journal of the American Chemical Society, 1986, vol. 108, # 22, p. 7114 - 7116
[2] Bulletin de la Societe Chimique de France, 1995, vol. 132, # 4, p. 428 - 452
[3] Farmaco, 1995, vol. 50, # 6, p. 455 - 469
[4] Synthesis, 2004, # 13, p. 2173 - 2180
[5] Bulletin de la Societe Chimique de France, 1988, # 4, p. 610 - 617
[6] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1987, p. 601 - 606
[7] Journal of Molecular Catalysis B: Enzymatic, 2010, vol. 66, # 1-2, p. 95 - 100
[8] Journal of Natural Products, 2016, vol. 79, # 7, p. 1783 - 1790
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  • [ 64201-03-2 ]
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Reference: [1] Photochemistry and Photobiology, 2007, vol. 83, # 3, p. 570 - 583
  • 20
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  • [ 95061-47-5 ]
Reference: [1] Chemische Berichte, 1988, vol. 121, p. 397 - 406
  • 21
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  • [ 391901-45-4 ]
Reference: [1] Patent: CN105481705, 2016, A,
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  • [ 274693-53-7 ]
Reference: [1] Patent: WO2012/142983, 2012, A1,
  • 23
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  • [ 376608-71-8 ]
YieldReaction ConditionsOperation in experiment
36.61%
Stage #1: With hydrogenchloride; zinc In methanol; water at -5 - 0℃;
Stage #2: With ammonia In dichloromethane; water at 30℃; for 0.25 h;
Stage #3: at 20 - 25℃;
Example 23; Preparation of trans-(lR,2S)-2-(3, 4-difluorophenyl)-cyclopropylamine (R)-(-)-mandelate salt; [0127] Trans-(lR,2S)-2-(3,4-difluorophenyl)-l-nitrocyclopropane (215.0 g) was added to the pre-cooled methanolic hydrochloric acid (6.0percent to 7percent w/w HC1, 4300 ml), followed by cooling the mass to -5 to 0°C. Zinc dust (343.71 g) was added to the resulting mass over a period of 2 to 3 hours while maintaining the temperature at -5 to 0°C. The reaction mass was stirred further for 2 hours at -5 to 0°C. After completion of the reaction, the reaction mass was filtered through a hyflo bed and the bed was washed with methanol (2 x 215 ml). The main filtrate and washings were combined, followed by distillation under reduced pressure. The resulting residue was dissolved in dichloromethane (1075 ml) and then cooled to 10 to 15°C. 25percent Aqueous ammonia solution (1290 ml) was added to the cooled solution while maintaining the temperature at below 30°C. The resulting reaction mass was stirred for 15 minutes, followed the by layer separation. The resulting aqueous layer was extracted with dichloromethane (2 x 537.5 ml) and then combined with the main dichloromethane layer. The combined dichloromethane layer containing the product was extracted thrice with aqueous hydrochloric acid (645 ml of cone, hydrochloric acid mixed with 1935 ml water, 3 x 865 ml). The aqueous acidic layer containing the product was combined and washed with dichloromethane (645 ml). Dichloromethane (1075 ml) was added to the acidic aqueous layer, followed by the addition of 25percent aqueous ammonia solution (1505 ml) while maintaining the temperature at below 30°C. The resulting reaction mass was extracted with dichloro methane (2 x 645 ml) and then combined with the main dichloromethane layer. The combined dichloromethane layer containing the product was washed with water (645 ml) and evaporated to dryness under reduced pressure. The resulting residue was dissolved in methanol (430 ml), followed slow addition of (R)-(-)-mandelic acid solution (107.5 g in 645 ml methanol) over a period of 40 to 60 minutes while maintaining temperature at 20 to 25 °C. The resulting slurry was stirred further for 12 hours at 20 to 25 °C, followed by further cooling to 0 to 5°C. The cooled solution was stirred for 2 hours and the solid was isolated by filtration. The resulting solid was washed with chilled methanol (215 ml). The solid was dried under reduced pressure at 40 to 45°C to obtain 127 g of pure trans- (lR,2S)-2-(3,4-difluorophenyl)-cyclopropylamine (R)-(-)-mandelate salt as a white solid (Yield : 36.61percent; HPLC Purity: 99.87percent by area; [R]25D = -97.0° (c 1, methanol)).
36.61%
Stage #1: With hydrogenchloride; zinc In deuteromethanol at -5 - 0℃;
Stage #2: at 0 - 25℃; for 14 h;
Example 22
Preparation of trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine (R)-(−)-mandelate salt
Trans-(1R,2S)-2-(3,4-difluorophenyl)-1-nitro cyclopropane (215.0 g) was added to the pre-cooled methanolic hydrochloric acid (6.0percent to 7percent w/w HCl, 4300 ml), followed by cooling the mass to −5 to 0° C. Zinc dust (343.71 g) was added to the resulting mass over a period of 2 to 3 hours while maintaining the temperature at −5 to 0° C. The reaction mass was stirred further for 2 hours at −5 to 0° C. After completion of the reaction, the reaction mass was filtered through a hyflo bed and the bed was washed with methanol (2×215 ml). The main filtrate and washings were combined, followed by distillation under reduced pressure. The resulting residue was dissolved in dichloromethane (1075 ml) and then cooled to 10 to 15° C. 25percent Aqueous ammonia solution (1290 ml) was added to the cooled solution while maintaining the temperature at below 30° C. The resulting reaction mass was stirred for 15 minutes, followed the by layer separation. The resulting aqueous layer was extracted with dichloromethane (2×537.5 ml) and then combined with the main dichloromethane layer. The combined dichloromethane layer containing the product was extracted thrice with aqueous hydrochloric acid (645 ml of conc. hydrochloric acid mixed with 1935 ml water, 3×865 ml). The aqueous acidic layer containing the product was combined and washed with dichloromethane (645 ml). Dichloromethane (1075 ml) was added to the acidic aqueous layer, followed by the addition of 25percent aqueous ammonia solution (1505 ml) while maintaining the temperature at below 30° C. The resulting reaction mass was extracted with dichloromethane (2×645 ml) and then combined with the main dichloromethane layer. The combined dichloromethane layer containing the product was washed with water (645 ml) and evaporated to dryness under reduced pressure. The resulting residue was dissolved in methanol (430 ml), followed slow addition of (R)-(−)-mandelic acid solution (107.5 g in 645 ml methanol) over a period of 40 to 60 minutes while maintaining temperature at 20 to 25° C. The resulting slurry was stirred further for 12 hours at 20 to 25° C., followed by further cooling to 0 to 5° C. The cooled solution was stirred for 2 hours and the solid was isolated by filtration. The resulting solid was washed with chilled methanol (215 ml). The solid was dried under reduced pressure at 40 to 45° C. to obtain 127 g of pure trans-(1R,2S)-2-(3,4-difluorophenyl)-cyclopropylamine (R)-(−)-mandelate salt as a white solid (Yield: 36.61percent; HPLC Purity: 99.87percent by area; [R]25D=−97.0° (c 1, methanol)).
Reference: [1] Patent: WO2011/132083, 2011, A2, . Location in patent: Page/Page column 39-40
[2] Patent: US2013/150577, 2013, A1, . Location in patent: Paragraph 0159
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YieldReaction ConditionsOperation in experiment
70.1% at 0 - 20℃; for 4 h; A solution of the compound of formula IX (1R, 2R) -2- (3,4-difluorophenyl) cyclopropyl formamide (3.5 g, 17.7 mmol)Was added 30percent sodium hydroxide (21.3 g, 160.0 mmol)5.2percent sodium hypochlorite (30.0 g, 21.0 mmol),Stirring at 25 to 40 degrees for 16 hours,Plus 50 ml of isopropyl acetate extraction,The oil phase was dried with anhydrous sodium sulfate,Was added dropwise to a solution of R-mandelic acid (2.7 g, 17.7 mmol) dissolved in 20 ml of isopropyl acetate,10 minutes drop finished,Stirred at room temperature for 1 hour,0 to 5 degrees stirring for 3 hours,filter,Cold isopropyl acetate wash,60 degrees decompression drying,To give the compound of formula II (1R, 2S) -2- (3,4-difluorophenyl) cyclopropylmethylamine-R-mandelate (4.0 g, 12.5 mmol). Yield 70.1percent.
46.4% at 20 - 25℃; for 14 h; 500ml four-necked flask was added compound (21.0g, 0.11mol) and 30percent aqueous sodium hydroxide solution (127.8g, 0.96mol). Under stirring, temperature at 0 ~ 5 , was added dropwise 10.5percent aqueous sodium hypochlorite solution (188.8g, 0.27mol), about 1h dropwise. After stirring at 0 ~ 5 continued until the reaction solution clarified rapidly warmed to 55 , reaction was continued for 1h. The reaction solution was cooled to 0 ~ 5 . Temperature not exceeding 10 , was added dropwise concentrated hydrochloric acid (about 100g) adjusted pH8 ~ 9. Was added dichloromethane (200ml), liquid separation. The aqueous layer (100ml × 2) and extracted with methylene chloride, the organic layers were combined, washed with water (200ml × 2). Dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to give a yellow oil compound (14.2g). Under stirring, temperature at 20 ~ 25 , methanol to the compound (60ml) was added dropwise a solution of D- mandelic acid (12.8g, 0.08mol) in methanol (76 ml of) solution dropwise for about 2h. At 20 ~ 25 , stirring was continued for 12h. Filtered cake was recrystallized from methanol to give a white solid compound (15.8g, 46.4percent), HPLC purity 99.7percent, ee value 99.9percent.
Reference: [1] Patent: CN104744266, 2017, B, . Location in patent: Paragraph 0089; 0090
[2] Patent: CN104974017, 2017, B, . Location in patent: Paragraph 0123-0126
[3] Patent: WO2012/85665, 2012, A2, . Location in patent: Page/Page column 48-49
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Reference: [1] Patent: CN107892693, 2018, A, . Location in patent: Paragraph 0035; 0060; 0062; 0064; 0104; 0145
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YieldReaction ConditionsOperation in experiment
7.56 g at 18 - 45℃; for 2.5 h; To a solution of 9 g R-mandelic acid in 300 ml of methanol at 45 C, was added a solution of 10 g of 2-(3.4-difluorophenyl)cyclopropanamine in 300 ml of methanol slowly over a period of 30 minutes. The reaction mixture was slowly cooled to 25 C, stirred for 1 h, then further cooled slowly to 18 C and maintained for another 1 h. The crystalized product was filtered off and washed with 20 ml of chilled methanol. The product was dried under vacuum to obtain 7.56 g of product as a white crystalline solid. 1H NMR in (400MHz, DMSO d6) 5 1 .13 -1 .16 (2H, m), 1.25 - 1.28 (2H, m), 2.20-2.23 (1 H, m), 2.65 - 2.67 (1 H, m), 4.64(1 H, s), 6.94 -6.96 (1 H, m). 7.1 1 -7.36 (8H, m)
Reference: [1] Patent: WO2013/144295, 2013, A1, . Location in patent: Page/Page column 25
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  • [ 29968-78-3 ]
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YieldReaction ConditionsOperation in experiment
84.3%
Stage #1: With Trimethyl borate In acetonitrile at 28 - 58℃; for 1.5 h;
Stage #2: With N-ethyl-N,N-diisopropylamine In acetonitrile at 58℃; for 12 h; Reflux
To a stirred solution of R-Mandelic acid (97.61 g) in acetonitrile (1000 mL), trimethylborate (66.66 g) was added at 28°C (±2). After addition of trimethylborate, reaction temperature was raised to 58°C (±2) and maintained for 90 minutes. To this solution, 2-(4-Nitro-phenyl)- ethylamine hydrochloride (NPA HCI) (100.0 g) was added at same temperature. To this solution, N, N-Diisopropylethyl amine (82.92 g) was added slowly and then reaction temperature was set to reflux for 12 hrs. The reaction temperature was lowered to 30°C (±2) and then diluted with ethyl acetate (1100 mL) and aqueous HCI (1M) solution (1400 mL). The separated organic layerwas washed successively with 1M hydrochloric acid aqueous solution. The organic layer was washed with 5percent sodium hydroxide aqueous solution and brine. The organic layer was concentrated in vacuo; the residue was recrystallized from toluene (500 mL). The solid was filtered, washed with toluene and dried under vacuo at 48°C (±2) to obtain pale yellow crystals of (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl] -2-phenylacetamide. VYield: 125 g (84.3percent); Purity by HPLC: 98.65percent.
80.03% With benzotriazol-1-ol; 1,2-dichloro-ethane; triethylamine In N,N-dimethyl-formamide at 30℃; for 6 h; (R) - mandelic acid (15.0g, 0.0986mol) and nitrobenzene hydrochloride (20.0g, 0.0986mol) in 75mlN, N- dimethyl formamide, stirring triethylamine, last added HOBT and EDC, 30 reaction 6h.TLC monitoring (GF254TLC plate, developing solvent: ethyl acetate: methanol = 5, if the heavy edges add 3 drops of triethylamine) to p-nitrophenyl ethylamine hydrochloride fluorescent spots disappear.Water was added and extracted with ethyl acetate, and concentrated under reduced pressure to remove ethyl acetate to give a yellow solid (III) 23.08g, yield: 80.03percent.
129.8 g With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 25 - 30℃; for 15 h; Example-1: Preparation of (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide (or) (Formula-4) (R)-2-hydroxy-2-phenylacetic acid compound of formula-2 (75 gms), triethylamine (49.8 gms), hydroxybenztriazole (HOBt) (66.6 gms) and l-ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride (EDC.HC1) (94.5 gms) were added to a mixture of 2-(4-nitrophenyl)ethylamine hydrochloride compound of formula-3a (100 gms) in N,N-dimethylformamide (370 ml) at 25-30°C and stirred for 15 hrs at the same temperature. Water (1860 ml) was added to the reaction mixture at 25-30°C and stirred for 30 mins at the same temperature. Ethyl acetate (1500 ml) was added to the reaction mixture at 25-30°C and stirred for 30 mins. Separated the both aqueous and organic layers and the organic layer was washed with 1M HCl solution, followed by 20percent (R)-2-hydroxy-N-(4-nitrophenethyl)-2-phenylacetamide aqueous potassium carbonate solution and finally with water. Distill off the solvent completely from the organic layer under reduced pressure. Toluene (600 ml) was added to the obtained compound, heated the reaction mixture to 80-85°C and stirred for 15 mins at the same temperature. Cooled the reaction mixture to 20-25°C and stirred for 12 hrs at the same temperature. Filtered the precipitated solid, washed with toluene and dried to get the title compound. Yield: 129.8 gms.
Reference: [1] Advanced Synthesis and Catalysis, 2017, vol. 359, # 20, p. 3665 - 3673
[2] Patent: WO2015/44965, 2015, A1, . Location in patent: Page/Page column 32
[3] Patent: CN105481705, 2016, A, . Location in patent: Paragraph 0017; 0018; 0019
[4] Patent: EP1440969, 2004, A1, . Location in patent: Page 5-6
[5] Patent: EP1559427, 2005, A1, . Location in patent: Page/Page column 5-6
[6] Patent: WO2014/132270, 2014, A2, . Location in patent: Page/Page column 17-18
[7] Patent: WO2016/24284, 2016, A2, . Location in patent: Page/Page column 28-29
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Reference: [1] Patent: EP1440969, 2004, A1, . Location in patent: Page 6
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Reference: [1] Patent: WO2016/24284, 2016, A2,
[2] Organic Process Research and Development, 2016, vol. 20, # 11, p. 1993 - 1996
[3] Organic Process Research and Development, 2016, vol. 20, # 11, p. 1993 - 1996
[4] Organic Process Research and Development, 2016, vol. 20, # 11, p. 1993 - 1996
[5] Acta Chimica Slovenica, 2018, vol. 65, # 1, p. 239 - 245
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Reference: [1] Patent: CN105481705, 2016, A,
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