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Chemical Structure| 623-33-6
Chemical Structure| 623-33-6
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Product Details of [ 623-33-6 ]

CAS No. :623-33-6 MDL No. :MFCD00012871
Formula : C4H10ClNO2 Boiling Point : -
Linear Structure Formula :- InChI Key :TXTWXQXDMWILOF-UHFFFAOYSA-N
M.W :139.58 Pubchem ID :2723640
Synonyms :
Glycine ethyl ester monohydrochloride

Calculated chemistry of [ 623-33-6 ]

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.75
Num. rotatable bonds : 3
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 32.3
TPSA : 52.32 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) : -6.89 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 0.37
Log Po/w (WLOGP) : 0.31
Log Po/w (MLOGP) : 0.01
Log Po/w (SILICOS-IT) : -0.41
Consensus Log Po/w : 0.06

Druglikeness

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

Water Solubility

Log S (ESOL) : -0.74
Solubility : 25.4 mg/ml ; 0.182 mol/l
Class : Very soluble
Log S (Ali) : -1.03
Solubility : 12.9 mg/ml ; 0.0925 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.33
Solubility : 64.8 mg/ml ; 0.465 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.03

Safety of [ 623-33-6 ]

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

Application In Synthesis of [ 623-33-6 ]

* 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 [ 623-33-6 ]
  • Downstream synthetic route of [ 623-33-6 ]

[ 623-33-6 ] Synthesis Path-Upstream   1~61

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Reference: [1] Journal of the Chemical Society, 1957, p. 1443
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  • [ 95-54-5 ]
  • [ 5805-57-2 ]
Reference: [1] Journal of the Chemical Society, 1957, p. 3313
  • 3
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  • [ 623-33-6 ]
  • [ 348-37-8 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 3, p. 511 - 514
[2] European Journal of Organic Chemistry, 2014, vol. 2014, # 3, p. 511 - 514
  • 4
  • [ 623-33-6 ]
  • [ 181294-58-6 ]
  • [ 5930-92-7 ]
Reference: [1] Journal of Organic Chemistry, 2004, vol. 69, # 24, p. 8382 - 8386
  • 5
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  • [ 34461-00-2 ]
  • [ 5930-92-7 ]
Reference: [1] Journal of Organic Chemistry, 1988, vol. 53, # 9, p. 1855 - 1859
  • 6
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  • [ 34461-00-2 ]
  • [ 5930-92-7 ]
Reference: [1] Journal of the Chemical Society, 1951, p. 3155,3172
  • 7
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  • [ 94569-84-3 ]
  • [ 348-36-7 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 3, p. 511 - 514
[2] European Journal of Organic Chemistry, 2014, vol. 2014, # 3, p. 511 - 514
  • 8
  • [ 174265-12-4 ]
  • [ 623-33-6 ]
  • [ 4792-67-0 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 3, p. 511 - 514
[2] European Journal of Organic Chemistry, 2014, vol. 2014, # 3, p. 511 - 514
  • 9
  • [ 623-33-6 ]
  • [ 98-86-2 ]
  • [ 13575-16-1 ]
Reference: [1] Chemical Communications, 2017, vol. 53, # 24, p. 3438 - 3441
  • 10
  • [ 5392-10-9 ]
  • [ 623-33-6 ]
  • [ 16382-18-6 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 3, p. 511 - 514
[2] European Journal of Organic Chemistry, 2014, vol. 2014, # 3, p. 511 - 514
  • 11
  • [ 623-33-6 ]
  • [ 14337-43-0 ]
YieldReaction ConditionsOperation in experiment
51% With hydrogenchloride; sodium nitrite In water at 0℃; for 1.16667 h; In 1 L round bottom flask equipped with stir bar added amino-acetic acid ethyl ester hydrochloride (20 g, 143 mmol) and water (30 ml). The solution was cooled down to [0°C] followed by sequential addition of concentrated hydrochloric acid (11.8 ml, 143 mmol) and dropwise addition of sodium nitrite (9. [89] g, 143 mmol) solution in water (15 ml). After 10 min added another equivalent each of concentrated hydrochloric acid and sodium nitrite solution in water. The reaction mixture was left stirring at [0°C] for 1 h. Reaction mixture was extracted with ether [(4X100] ml). Combined organic phase was dried (sodium sulfate), filtered and concentrated in-vacuo to isolate a lemon yellow solid. The solid was recrystallized from hexanes to isolate a white solid (11 g, 51percent). 1H-NMR [(CDC13),] d (ppm): 9.98 (bs, 1H), 4.40 (q, 2H), 1. 38 (t, 3H).
49.9% at 0 - 5℃; for 0.916667 h; EXAMPLE 4; 5-5chloro-2-fluorophenyl)isoxazole-3-carbaldehyde; (i) ethyl chloro(hydroxyimino)acetate; Concentrated hydrochloric acid (5.9 ml, 71.65 mmol) was added in a drop-wise manner to a solution of glycine ethyl ester hydrochloride (10 g, 71.65 mmol) in water (15 ml) at 0° C. Sodium nitrite (4.94 g, 71.65 mmol) in water (7.5 ml) was then added in a drop-wise manner to the resulting mixture, keeping the temperature below 5° C. After 10 min., the second equivalent of hydrochloric acid (5.9 ml, 71.65 mmol) as added drop-wise, followed by sodium nitrite (4.94 g, 71.65 mmol) in water (7.5 ml), again keeping the temperature below 5° C. The reaction mixture was stirred at 0° C. for 45 min., and then washed with ether. The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo to yield a yellow solid. The solid was recrystallized from hexanes, filtered and washed with hexanes to isolate a white crystalline solid (5.4153 g, 49.9percent). 1H NMR (300 MHz, CDCl3): δ (ppm) 9.01 (s, 1H); 4.42(q, 2H); 1.41 (t, 3H).
44% at -5℃; A. Synthesis of ethyl chloro(hydroxyirnino)acetate (C87). Ethyl 2-aminoacetate hydrochloride (40 g, 286.57 mmol) was added to a solution of water (54 ml) and concentrated hydrochloric acid (36 mL) and the reaction was cooled to -5°C. The solution was then treated drop-wise with a solution of sodium nitrite (19.77 g, 286.57 mmol) in water(36 ml) while maintaining the reaction temperature below -5°C, The mixture was stirred for 0.5 h and treated with another portion of concentrated hydrochloric acid (36 ml) followed by the drop-wise addition of a solution of sodium nitrite (19.77 g, 286.57 mmol) in water (36 mL). The reaction was further stirred for 2 h at -5°C. The mixture was then extracted with diethyl ether (400 mL). The resultant organic layer was collected, washed with water (100 mL), saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate and concentrated, The resultant residue was recrystallized from hexanes to provide C87 as a white solid. Yield; 19.10 g, 44percent, 1H-NMR (400 MHz, CDCb) 9.76 (1H, bι. s), 4.41 (2H, q), 1.40 (3H, t).
39% With hydrogenchloride; sodium nitrite In water at -5℃; Step 1
Ethyl chlorooximidoacetate
A 250 mL round bottom flask was charged with glycine ethyl ester hydrochloride (40 g, 0.29 mol), concentrated HCl (24 mL, 0.29 mol) and water (55 mL).
To the above was added dropwise a solution of sodium nitrite (20 g, 0.29 mol) in water (30 mL) at -5° C.
A second equivalent of hydrochloric acid and sodium nitrite were then added in the same manner.
The resulting mixture was stirred at -5° C. for 20 min then extracted with ethyl ether (250 mL).
The extract was dried over anhydrous MgSO4 and concentrated in vacuo.
The yellowish oil residue was crystallized from hexane to afford 17 g (39percent) of the product as white crystals. 1H NMR (300 MHz, CDCl3) δ: 9.92 (br, 1H), 4.39 (q, J=7.1 Hz, 2H), 1.38 (t, J=7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3) δ: 158.5, 132.9, 63.8, 13.9.
39% With hydrogenchloride; sodium nitrite In water at -5℃; for 0.333333 h; A 250 mL round bottom flask was charged with glycine ethyl ester hydrochloride (40 g, 0.29 mol), concentrated HCl (24 mL, 0.29 mol) and water (55 mL). To the above was added dropwise a solution of sodium nitrite (20 g, 0.29 mol) in water (30 mL) at -5 °C. A second equivalent of hydrochloric acid and sodium nitrite were then added in the same manner. The resulting mixture was stirred at -5 °C for 20 min then extracted with ethyl ether (250 mL). The extract was dried over anhydrous MgS04 and concentrated in vacuo. The yellowish oil residue was crystallized from hexane to afford 17 g (39percent) of the product as white crystals. JHNMR (300 MHz, CDC13) δ: 9.92 (br, 1H), 4.39 (q, J = 7.1 Hz, 2H), 1.38 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz, CDC13) δ: 158.5, 132.9, 63.8, 13.9
36.9%
Stage #1: With hydrogenchloride In water at 0 - 10℃; for 0.5 - 1 h;
Stage #2: With sodium nitrite In water at -5 - 5℃; for 3 h;
EXAMPLE 11Laboratory-Scale Production of ECHAEthyl chlorohydroxyiminoacetate (ECHA) can be produced from glycine ethyl ester hydrochloride by the in-situ generation of nitrosyl chloride gas from aqueous sodium nitrite and HCl. In particular, Glycine ethyl ester.HCl is dissolved in water. To this is added concentrated HCl solution (32percent) and the reaction mixture is cooled to <10° C. HCl gas is then bubbled into the reaction mixture. An aqueous solution of sodium nitrite is dosed into the reactor while maintaining the temperature at <10° C. HCl gas is bubbled into the reactor again followed by a second portion of aqueous sodium nitrite. Finally, the product is purified from the reaction mixture by any appropriate means known to those of skill in the art. For example, the reaction mixture is stirred for a further period and then extracted with a water immiscible solvent (dichloroethane, chloroform, carbon tetrachloride) at room temperature to remove the product from the reaction mixture. The organic extracts are dried with a drying agent and the solvent is flashed off. An oily residue remains, which crystallizes on cooling. The crystals are filtered and washed with a suitable solvent to obtain a purified ECHA.EXAMPLE 12Large-Scale Production of ECHAGlycine ethyl ester hydrochloride (6.3 kg, 0.045 kmol) was dissolved in hydrochloric acid (32percent, 5.13 kg). The solution was cooled to 0° C. and hydrochloric acid gas was bubbled into the reactor via a sparging tube for 1 hour while maintaining the temperature at <5° C. The reaction mixture was then cooled to -5° C. A solution of sodium nitrite (3.11 kg) in water (4.5 L) was then dosed into the reactor using a diaphragm pump while maintaining the temperature at -5° C. to 0° C. This operation was complete within an hour. A second portion of gaseous HCl was sparged into the reactor over 1 hour at 0 to 5° C. This was followed by a second portion of sodium nitrite (3.11 kg) in water (4.5 L) which was added over one hour while maintaining the temperature at -5° C. to 0° C. The reaction mixture was stirred for a further hour and was then extracted with chloroform (3.x.2 kg) at ambient temperature. The organic extracts were combined, dried (MgSO4) and evaporated in-vacuo (40° C.). An oily residue remained which crystallized upon cooling to ambient temperature. The crystals were filtered and washed with hexane (2 kg) at 5° C. The crystals were dried under vacuum to obtain a pure (by NMR), white product (2.53 kg, 36.9percent). The yield of ECHA over 10 runs ranged from 31.4 to 51.2percent at an average of 39.8percent.EXAMPLE 13Laboratory-Scale Preparation of ECHAReactions were carried out in a 1 L, jacketed, baffled reactor equipped with an overhead mechanical propeller-type stirrer and a sparging tube positioned below the surface of the reaction mixture. Glycine ethyl ester hydrochloride (210 g, 1.50 moles) was dissolved in water (270 mL) and added to the reactor. To this was added hydrochloric acid (32percent, 54.7 g, 1.52 moles). The solution was cooled to 0° C. and hydrochloric acid gas was bubbled for 30 minutes into the reactor via the sparging tube. The gas was generated by adding aqueous hydrochloric acid (32percent, 100 mL) to concentrated sulfuric acid (98percent, 100 mL) using a dropping funnel while maintaining the temperature of the acid mixture at less than 5° C. The reaction mixture was then cooled to -5° C. A solution of sodium nitrite (103.5 g, 1.50 moles) in water (150 mL) was then dosed into the reactor using a diaphragm pump while maintaining the temperature at -5° C. to 0° C. This operation was complete within an hour. A second portion of gaseous HCl (ex. 100 mL HCl and 100 mL H2SO4) was sparged into the reactor over 30 minutes at 0 to 5° C. This was followed by a second portion of sodium nitrite (103.5 g, 1.50 moles) in water (150 mL) which was added over one hour while maintaining the temperature at -5° C. to 0° C. The reaction mixture was stirred for a further 30 minutes and was then extracted with chloroform (3.x.200 mL) at ambient temperature. The organic extracts were combined, dried (MgSO4) and evaporated in-vacuo (40° C.). An oily residue remained which crystallized upon cooling to ambient temperature. The crystals (192.4 g) were stirred with hexane (200 mL) at 5° C. for 1 hour and then filtered. The crystals were dried under vacuum to afford the ethyl chlorohydroxyiminoacetate product (122.1 g, 0.81 moles, 53.9percent).

Reference: [1] Journal of Organic Chemistry, 1983, vol. 48, # 3, p. 366 - 372
[2] Tetrahedron, 2001, vol. 57, # 38, p. 8039 - 8046
[3] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 8, p. 2347 - 2350
[4] Patent: WO2004/14881, 2004, A2, . Location in patent: Page 166
[5] Patent: US2007/37820, 2007, A1, . Location in patent: Page/Page column 16
[6] Patent: WO2010/32147, 2010, A2, . Location in patent: Page/Page column 85
[7] Patent: US2010/120741, 2010, A1, . Location in patent: Page/Page column 102
[8] Patent: WO2011/112731, 2011, A2, . Location in patent: Page/Page column 215
[9] Synlett, 2011, # 8, p. 1154 - 1156
[10] Patent: US2009/88577, 2009, A1, . Location in patent: Page/Page column 9-10; sheet 1; 4
[11] Organic Process Research and Development, 2011, vol. 15, # 1, p. 249 - 257
[12] Journal of the American Chemical Society, 1924, vol. 46, p. 739
[13] Journal of the Chemical Society - Perkin Transactions 1, 1996, # 12, p. 1319 - 1321
[14] Tetrahedron, 2009, vol. 65, # 51, p. 10679 - 10684
[15] Journal of Biological Chemistry, 2011, vol. 286, # 22, p. 19422 - 19430
[16] Patent: WO2014/127315, 2014, A1, . Location in patent: Page/Page column 52
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  • [ 144-55-8 ]
  • [ 14337-43-0 ]
YieldReaction ConditionsOperation in experiment
1.749 g
Stage #1: With hydrogenchloride; sodium nitrite In water at -5 - 20℃; for 26 h;
Stage #2: at 20℃;
To a 200 mL round bottom flask glycine ethyl ester hyrochloride (35.8 mmol, 5.0 g) cooled to -5 °C 5.9 mL of 12M HCl were added and followed by addition of NaNO2 (71.6 mmol, 4.94 g). The reaction was stirred at -5 °C for 2 hours, then was allowed to warm to r.t. over 24 hours. The solution was diluted with NaHCO3 to a pH of 3-4. The product was then extracted with 15 mL EtOAc three times. The yellow liquid was dried with MgSO4 and concentrated under reduced pressure. The material was carried on to the next reaction step without further purification as a yellowish oil (1,749 g). Visualization was done using UV TLC: Solvent: 3:1 Hexanes:EtOAc, Rf= 0.53.
Reference: [1] Tetrahedron Letters, 2011, vol. 52, # 43, p. 5656 - 5658
  • 13
  • [ 623-33-6 ]
  • [ 22356-89-4 ]
YieldReaction ConditionsOperation in experiment
77%
Stage #1: With methylamine In ethanol at 50℃; for 0.5 h;
Stage #2: With sodium hydroxide In ethanol at 50℃; for 0.05 h;
Glycine ethyl ester hydrochloride (5.23 g, 37.5 mmol) was stirred in a 33percent w/w ethanolic solution of methylamine (25 mL, 6.24 g, 201 mmol) at 50 °C for 30 min before sodium hydroxide (1.61 g, 40.4 mmol) was added and stirring continued for 3 min. The mixture was evaporated to give a slurry then extracted with ethyl acetate (2.x.50 mL), which was filtered and removed in vacuo to yield the desired product, a clear oil (2.56 g, 29.1 mmol, 77percent); νmax (NaCl disk)/cm-1 3353, 3101, 2947, 1659, 1564, 1414, 1312, 1161; δH (500 MHz, DMSO;d6) 7.79 (1H, br s, CONH), 3.06 (2H, s, CH2), 2.61 (3H, d, J 4.7, CH3), 1.89 (2H, s, NH2); δC (125 MHz, DMSO;d6) 173.9 (C), 45.3 (CH2), 25.7 (CH3); m/z (EI+): 88.1 (M+); HRMS (EI+): found M+H+, 88.0634. C3H8N2O1 requires, 88.0637.
Reference: [1] Tetrahedron, 2011, vol. 67, # 23, p. 4263 - 4267
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  • [ 74-89-5 ]
  • [ 22356-89-4 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 22, p. 4884 - 4896
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  • [ 623-33-6 ]
  • [ 124-40-3 ]
  • [ 22356-89-4 ]
Reference: [1] Helvetica Chimica Acta, 1985, vol. 68, p. 135 - 143
  • 16
  • [ 623-33-6 ]
  • [ 149-73-5 ]
  • [ 2491-15-8 ]
Reference: [1] Chemical Communications, 2008, # 26, p. 3001 - 3003
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  • [ 79-22-1 ]
  • [ 5602-94-8 ]
Reference: [1] Journal of Organic Chemistry, 1990, vol. 55, # 3, p. 918 - 924
[2] Chemical Communications, 2009, # 26, p. 3925 - 3927
[3] Synthetic Communications, 1992, vol. 22, # 9, p. 1249 - 1258
[4] Chemische Berichte, 1906, vol. 39, p. 858
[5] Journal of Medicinal and Pharmaceutical Chemistry, 1962, vol. 5, p. 752 - 762
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  • [ 623-33-6 ]
  • [ 53921-04-3 ]
  • [ 5602-94-8 ]
Reference: [1] Tetrahedron, 1998, vol. 54, # 49, p. 14679 - 14688
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  • [ 75-44-5 ]
  • [ 623-33-6 ]
  • [ 5602-94-8 ]
Reference: [1] Patent: US4491548, 1985, A,
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  • [ 105-36-2 ]
  • [ 6290-05-7 ]
Reference: [1] Farmaco, Edizione Scientifica, 1977, vol. 32, # 8, p. 602 - 613
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  • [ 4755-77-5 ]
  • [ 29655-79-6 ]
YieldReaction ConditionsOperation in experiment
51% With triethylamine In dichloromethane Example 2 Ii; Compound 4 was prepared according to the Ref: J. Hetero. Chem. 1995, 32, 1693-1702. Then, it was reduced by NaBH4ZLiCl in ethanol solution. Further oxidation by Dess-Martin reagent gave the desired aldehyde 6 in 25 percent overall two-step yield.
Reference: [1] Synthetic Communications, 2000, vol. 30, # 17, p. 3171 - 3180
[2] Patent: WO2007/124546, 2007, A1, . Location in patent: Page/Page column 63
[3] Chemische Berichte, 1897, vol. 30, p. 590
[4] Journal of the American Chemical Society, 1997, vol. 119, # 1, p. 86 - 93
[5] Organic Process Research and Development, 2004, vol. 8, # 2, p. 192 - 200
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  • [ 95-92-1 ]
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Reference: [1] Journal of Heterocyclic Chemistry, 1995, vol. 32, # 6, p. 1693 - 1702
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  • [ 244205-40-1 ]
  • [ 2178-24-7 ]
Reference: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 39, p. 10510 - 10514[2] Angew. Chem., 2014, vol. 126, # 39, p. 10678 - 10682,5
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  • [ 69555-14-2 ]
YieldReaction ConditionsOperation in experiment
91%
Stage #1: With toluene-4-sulfonic acid In toluene at 110 - 115℃; for 4 h;
Stage #2: With N-ethyl-N,N-diisopropylamine In toluene for 1 h;
Example 1 : Preparation of benzophenone glycine imine ethyl ester. In a 1 litre glass reactor equipped with a distillation section and a Dean and Stark separator, 182g (1 mole) of benzophenone, 70.1g (0.5 mole) of glycine ethyl ester hydrochloride, 4.75g (0.05 mole) of paratoluenesulfonic acid and 249g of toluene were loaded. The mixture was heated at 110-115°C at atmospheric pressure to give a good reflux in toluene. 97g (1.05 mole) of N,N-diisopropyl N-ethyl amine was added by pump over 4 hours. During the reaction, water was formed and was distilled off as water-toluene azeotrop. Water was decanted in the Dean and Stark seprator and toluene was returned to the reactor. Reaction was pursued for 1 hour after the end of the amine addition and completion of the reaction was monitored by liquid chromatography. When reaction was complete, the reaction mixture was cooled down to 20°C. The mixture was then washed with 335g of water and the 2 liquid phases were separated by decantation. The bottom aqueous phase containing all N,N-diisopropyl N-ethyl amine hydrochloride was kept for treatment by aqueous sodium hydroxide to recover N,N-diisopropyl N-ethyl amine for recycle. The upper toluen phase containing benzophenone glycine imine ethyl ester and the excess benzophenone was concentrated during which operation water was removed as an azeotrope with toluene. The dry solution, of benzophenone glycine imine ethyl ester in toluene was assayed by liquid chromatography : a 91 percent yield of benzophenone glycine imine ethyl ester was obtained with respect to glycine ethyl ester hydrochloride.
48%
Stage #1: With potassium carbonate In water for 0.25 h;
Stage #2: With boron trifluoride diethyl etherate In xylene for 5 h; Reflux
2.1
Preparation of ethyl N-(diphenylmethylene)glycinate
Ethyl glycinate hydrochloride (37 g, 0.27 mol) was dissolved in a solution of K2CO3 (74.4 g, 0.54 mol) in water (186 ml).
The solution was stirred for 15 min and then extracted with dichloromethane (10*150 ml).
The organic phases obtained in this manner were combined, dried over MgSO4 and freed from solvent under reduced pressure (500 mbar) (yield ~50percent).
The residue (9.5 g, 0.092 mol) was, together with benzophenone (14.03 g, 0.077 mol) dissolved in xylene (76 ml).
After addition of a few drops of BF3*Et20, the reaction mixture was stirred under reflux conditions on a water separator for 5 h.
After cooling of the reaction mixture to room temperature, the solvent was removed under reduced pressure.
From the residue obtained, ethyl N-(diphenylmethylene)glycinate was isolated by distillation (80° C. at 5.5*10-2 mbar) in a yield of 48percent.
30%
Stage #1: With toluene-4-sulfonic acid In toluene at 115℃; Dean-Stark
Stage #2: With N-ethyl-N,N-diisopropylamine In toluene for 18.75 h;
Step 3: To a 500 mL three neck RB flask equipped with a distillation and a Dean-Stark separator, benzophenone (20 g, 109.8 mmol), glycine ethyl ester Hydrochloride (15.32 g, 109.8mmol), p-toluenesulfonic acid (0.522 g, 2.745 mmol) and 400 mL of toluene were added. The mixture was heated at 115 C with stirring to get a good reflux in toluene. Finally N, Ndiisopropyl ethyl amine (14.4 mL, 82.35 mmole) was added using a dropping funnel over 45 mm. During the reaction, water was formed which was decanted from the Dean-Stark separator and toluene were returned to the reactor. The reaction was monitored by TLC, and it took about18 h for 50percent completion. The reaction mixture was cooled down to room temperature, and extracted (3 x 100 mL) with ethyl acetate, collected organic layer and washed organic layer once with saturated NaCI solution. The organic layer separated, dried over Na2504, and distilled off the volatiles to get crude material, which was flash chromatographed to get 9.0 g (30percent isolated) ofEthyl-2-(diphenylmethyleneamino) acetate as a white solid, which was confirmedbyH1NMR.
Reference: [1] Patent: EP1422220, 2004, A1, . Location in patent: Page 5
[2] Patent: CN104557684, 2017, B, . Location in patent: Paragraph 0021-0026; 0027; 0028; 0029; 0030-0033
[3] Tetrahedron Letters, 2005, vol. 46, # 16, p. 2795 - 2797
[4] Patent: US2010/173777, 2010, A1, . Location in patent: Page/Page column 23
[5] Patent: WO2016/27285, 2016, A2, . Location in patent: Page/Page column 50; 51
[6] Patent: US2010/190794, 2010, A1, . Location in patent: Page/Page column 59
[7] Organic Letters, 2012, vol. 14, # 2, p. 552 - 555
[8] Angewandte Chemie - International Edition, 2013, vol. 52, # 49, p. 12942 - 12945[9] Angew. Chem., 2013, vol. 125, # 49, p. 13180 - 13183,4
[10] Patent: CN104788361, 2017, B, . Location in patent: Paragraph 0054-0056
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  • [ 1013-88-3 ]
  • [ 623-33-6 ]
  • [ 69555-14-2 ]
YieldReaction ConditionsOperation in experiment
97% at 20℃; for 18 h; Glycine ethyl ester hydrochloride (1.00 g, 7.16 mmol) was dissolved in dry DCM (40 ml). Benzophenone imine (1.20 ml, 7.16 mmol) was added dropwise. The RM was stirred at rt for 18 h. The RM was filtered through Celite, washed with DCM and the filtrate concentrated in vacuo. The resulting oil was triturated with hexane to give the desired product as a white solid.Y = 97 percent MS ES+: 268.
74% at 20℃; General Procedure A; Preparation of Amino Ester Ketimine from Amino Ester Hydrochloride; Referring to FIG. 6 in the attached drawings, glycine ethyl ester hydrochloride 14b (2.015 g, 14.4 mmol) was suspended in 25 mL dry DCM (dichloromethane) and benzophenone imine (2.42 mL, 14.4 mmol) was added and stirred at room temperature for 8-16 hr. The reaction mixture was filtered, washed with 5 mL DCM and the organic solution was washed 1.x. with H2O and 1.x. with brine (a saturated aqueous solution of sodium chloride). The DCM was dried by filtering over a bed of Hydromatrix brand diatomaceous earth and concentrating to dryness in vacuo. The product 16b, an oil (2.83 g, 74percent), was used without further purification. MS (LC/MS, ESI): 268 (M+H). 1H NMR (300 MHz, CDCl3, δ): 7.5-8.0 (m, 10H), 4.5 (s, 2H), 4.0 (q, 2H), 1.2 (t, 3H). See, O'Donnell et al., J. Org. Chem. 47, 2663 (1982).
Reference: [1] European Journal of Organic Chemistry, 2015, vol. 2015, # 27, p. 5949 - 5958
[2] Journal of Organic Chemistry, 1982, vol. 47, # 13, p. 2663 - 2666
[3] Patent: WO2018/167468, 2018, A1, . Location in patent: Page/Page column 76
[4] Chemical Communications, 1998, # 16, p. 1679 - 1680
[5] Tetrahedron Letters, 1999, vol. 40, # 32, p. 5841 - 5844
[6] Journal of Chemical Research, Miniprint, 1996, # 11, p. 2768 - 2792
[7] Patent: US6268363, 2001, B1,
[8] Patent: US2010/189644, 2010, A1, . Location in patent: Page/Page column 21
[9] Patent: US5198548, 1993, A,
[10] Chinese Chemical Letters, 2013, vol. 24, # 2, p. 120 - 122
  • 26
  • [ 24424-99-5 ]
  • [ 623-33-6 ]
  • [ 14719-37-0 ]
YieldReaction ConditionsOperation in experiment
98% With triethylamine In tetrahydrofuran at 0℃; for 36 h; 1.Ethyl 2-[(tert-butoxy)carbonylamino]acetate (5)
Di-tert-butyl dicarbonate (365 g, 1.67 mol) in tetrahydrofuran (1L) is added dropwise to a 0° C. solution of glycine ethyl ester hydrochloride (232.5 g, 1.66 mol) and triethylamine (497.5 ml, 3.57 mol) in tetrahydrofuran (2.5 L.) The reaction mixture is vigorously stirred for 36 hours and then filtered.The filtrate is the concentrated in vacuo to afford 329.4 9 (98percent) of compound 5 as a white solid.
63% With sodium hydroxide In 1,4-dioxane; water at 20℃; for 2 h; A solution of di-tert-butyl dicarbonate (5.14 g, 23.5 mmol) in dioxane (7 mL) was added dropwise to a stirred solution of glycine ethyl ester hydrochloride 4 (3.02 g, 21.6 mmol) in water (60 mL) at 0 °C. After being left to stir for a further 15 min at this temperature, the reaction was allowed to warm slowly to rt whilst the pH was maintained at 10.5 by the addition of 2 M(aq) NaOH. After 2 h, the reaction mixture was concentrated in vacuo and the residual paste was dissolved in CH2Cl2 (50 mL). The resulting organic solution was washed with water (20 mL), the two phases were separated and the aqueous layer was re-extracted with CH2Cl2 (30 mL). The combined organic layers were dried (MgSO4) and the solvent was evaporated under reduced pressure. The crude product obtained was purified by column chromatography (EtOAc/petroleum ether (40-60 °C), 6:4) to afford N-Boc-glycine ethyl ester (2.77 g, 63percent) as a yellow liquid; Rf 0.66 (EtOAc/petroleum ether (40-60 °C), 6:4); δH (200 MHz; CDCl3) 1.22 (2H, t, J 7.2, OCH2CH3), 1.39 (9H, s, C(CH3)3), 3.83 (2H, d, J 5.6, NHCH2CO), 4.10 (2H, q, J 7.2, OCH2CH3), 5.04 (1H, br s, NH); δC (50 MHz; CDCl3) 14.0, 28.2, 42.3, 61.1, 79.6, 155.7, 170.3; m/z (CI) 204 ([M+H]+, 20percent),165 (90), 104 (100), 58 (10), 44 (16); HRMS (ESI) m/z: [M+H]+, found 204.1230. C9H18NO4 requires 204.1230.
Reference: [1] Chemical Communications, 2009, # 26, p. 3925 - 3927
[2] Journal of the American Chemical Society, 2006, vol. 128, # 33, p. 10638 - 10639
[3] Patent: US2004/19215, 2004, A1, . Location in patent: Page 6
[4] Synthetic Communications, 1992, vol. 22, # 9, p. 1249 - 1258
[5] Tetrahedron Letters, 2006, vol. 47, # 43, p. 7551 - 7556
[6] Tetrahedron, 2011, vol. 67, # 49, p. 9588 - 9594
[7] Journal of the Chemical Society - Perkin Transactions 1, 1999, # 19, p. 2713 - 2723
[8] Tetrahedron Letters, 2007, vol. 48, # 29, p. 5023 - 5026
  • 27
  • [ 623-33-6 ]
  • [ 14719-37-0 ]
YieldReaction ConditionsOperation in experiment
91% With triethylamine In dichloromethane at 38 - 40℃; General procedure: L-Phenylalanine methyl ester hydrochloride (5.0 g, 23.2 mmol), triethyl amine (2.47 g, 24.4 mmol) and 2 (7.24 g, 24.4 mmol) were added to dichloromethane (50 mL) and stirred at reflux temp (38-40°C) for 5h. After completion of the reaction, filtered to remove salts and the filtrate was washed with 5percent KHSO4 (20 mL), water (25 mL), brine (25 mL), and dried over sodium sulfate. The solvent was evaporated under reduced pressure to obtain a pale yellow oil. The oil was purified by column chromatography (silica gel, ethyl acetate/ hexane, 8:2) to afford 5.96 g (92percent) Methyl (tert-butoxycarbonyl)-L-phenylalaninate as a colorless oil.
Reference: [1] Synthetic Communications, 2017, vol. 47, # 22, p. 2127 - 2132
  • 28
  • [ 623-33-6 ]
  • [ 219580-32-2 ]
  • [ 14719-37-0 ]
Reference: [1] Tetrahedron, 1998, vol. 54, # 49, p. 14679 - 14688
  • 29
  • [ 623-33-6 ]
  • [ 219580-24-2 ]
  • [ 14719-37-0 ]
Reference: [1] Tetrahedron, 1998, vol. 54, # 49, p. 14679 - 14688
  • 30
  • [ 5467-74-3 ]
  • [ 623-33-6 ]
  • [ 14062-25-0 ]
Reference: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 39, p. 10510 - 10514[2] Angew. Chem., 2014, vol. 126, # 39, p. 10678 - 10682,5
  • 31
  • [ 24424-99-5 ]
  • [ 623-33-6 ]
  • [ 6926-09-6 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1994, # 12, p. 1595 - 1600
  • 32
  • [ 623-33-6 ]
  • [ 126747-14-6 ]
  • [ 1528-41-2 ]
Reference: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 39, p. 10510 - 10514[2] Angew. Chem., 2014, vol. 126, # 39, p. 10678 - 10682,5
  • 33
  • [ 89598-96-9 ]
  • [ 623-33-6 ]
  • [ 14062-30-7 ]
Reference: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 39, p. 10510 - 10514[2] Angew. Chem., 2014, vol. 126, # 39, p. 10678 - 10682,5
  • 34
  • [ 128796-39-4 ]
  • [ 623-33-6 ]
  • [ 721-63-1 ]
Reference: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 39, p. 10510 - 10514[2] Angew. Chem., 2014, vol. 126, # 39, p. 10678 - 10682,5
  • 35
  • [ 24424-99-5 ]
  • [ 623-33-6 ]
  • [ 149794-10-5 ]
Reference: [1] Patent: US2008/125614, 2008, A1,
  • 36
  • [ 64-17-5 ]
  • [ 56-40-6 ]
  • [ 623-33-6 ]
YieldReaction ConditionsOperation in experiment
90.4% at -10 - 20℃; for 2 h; Heating / reflux 247.3 g of thionyl chloride and 130 g of glycine were added at -10 C. to 1000 ml of ethanol. After removing the ice bath a further equivalent amount of glycine was added in portions. The mixture was then stirred for 2 hours under reflux. After cooling to room temperature the excess alcohol and the thionyl chloride were removed on a rotary evaporator. Ethanol was added twice more to the white solid obtained and the ethanol was in turn removed on the rotary evaporator in order completely to remove adhering thionyl chloride. After recrystallisation from ethanol 218.6 g (90.4percent of theory) of the title compound (product 2) were obtained.
90.48% Reflux 3.00 g of glycine (0.04 mol) was dissolved in 50 mL of ethanol, and 7.14 g (0.06 mol) of thionyl chloride was slowly added dropwise at a temperature of 20 DEG C. After the addition was complete, the reaction was refluxed overnight. After the reaction was over, the solvent was distilled off to give 5.04 g of an off-white solid. Yield: 90.48percent.
88.98%
Stage #1: at -5 - 5℃; for 1 h;
Stage #2: at 70℃; for 5 h;
Control the temperature of -5 ~ 5 ° C, acetyl chloride 23.56g drop by dropwise to anhydrous ethanol70ml, after the drip reaction lh, divided into two batches of glycine 7.5lg, add the system temperature to 70 ° C reaction 5h, decompression concentratedRemove the excess solvent, the residue and then add acetone 40ml stirring 5h, filter, filter cake vacuum drying to glycine ethyl ester hydrochloric acidSalt 12.22 g, yield 88 • 98percent, m.p. 142-144 ° C.
84% at 0 - 20℃; for 16 h; Step 1; Synthesis of ethyl aminoacetate hydrochloride: To a stirred solution of glycine (40 g, 0.53 mol) in ethanol (400 ml), thionyl chloride (158.49 g, 1.33 mol) was added drop-wise at 0°C. The reaction mixture was allowed to warm to room temperature and stirring continued further for 16 hours at room temperature. The resulting mixture was concentrated under reduced pressure. The residual syrup was diluted with diethyl ether (200 ml) and then stirred for 15 minutes. The separated solid was filtered and washed with additional diethyl ether (40 ml). The solid was quickly transferred to a round bottom flask and dried under reduced pressure to obtain 62 g of ethyl aminoacetate hydrochloride white solid in 84percent yield.
33.4 g
Stage #1: at 0 - 25℃;
Stage #2: at 25℃;
(1) Add 250 mL of anhydrous ethanol to a 500 mL three-necked flask,Then 36.2 mL (0.5 mol) of SOCl2 was added dropwise under an ice bath,The reaction temperature was controlled at 0-5 ° C,Reaction was colorless at this time, the reaction system temperature, SOCl2 plus Bi,The reaction was shifted to room temperature (25 ° C)At this point the reaction system showed white turbidity, room temperature reaction 2-3h,Then 18.8 g (0.25 mol) of glycine was added in one portion,Reaction at room temperature 25 10-12h. Reaction post-treatment,And filtered through suction to obtain 33.4 g of the formula (2) as a milky white solid.

Reference: [1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 8, p. 1942 - 1944
[2] Patent: US2003/236253, 2003, A1, . Location in patent: Page 12
[3] Patent: CN107652265, 2018, A, . Location in patent: Paragraph 0040; 0041
[4] Journal of Medicinal Chemistry, 2012, vol. 55, # 1, p. 55 - 67
[5] Patent: CN105820102, 2016, A, . Location in patent: Paragraph 0038
[6] Patent: WO2017/2087, 2017, A1, . Location in patent: Page/Page column 19
[7] Tetrahedron, 1990, vol. 46, # 15, p. 5325 - 5332
[8] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 6, p. 2336 - 2350
[9] European Journal of Medicinal Chemistry, 2011, vol. 46, # 1, p. 11 - 20
[10] Chinese Journal of Chemistry, 2011, vol. 29, # 5, p. 1011 - 1016
[11] Journal of Labelled Compounds and Radiopharmaceuticals, 2011, vol. 54, # 14, p. 855 - 858
[12] Nucleosides, Nucleotides and Nucleic Acids, 2013, vol. 32, # 4, p. 161 - 173
[13] Chinese Chemical Letters, 2013, vol. 24, # 2, p. 120 - 122
[14] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 5, p. 1067 - 1070
[15] Russian Journal of Organic Chemistry, 2014, vol. 50, # 12, p. 1732 - 1737[16] Zhurnal Organicheskoi Khimii, 2014, vol. 50, # 12, p. 1750 - 1756,7
[17] Tetrahedron Letters, 2016, vol. 57, # 31, p. 3444 - 3448
[18] Patent: CN103242187, 2016, B, . Location in patent: Paragraph 0037
[19] Patent: CN104072498, 2016, B, . Location in patent: Paragraph 0054; 0083; 0096; 0146
[20] Journal of Medicinal Chemistry, 2018, vol. 61, # 7, p. 2707 - 2724
[21] Food Chemistry, 2018, vol. 268, p. 220 - 232
  • 37
  • [ 56-40-6 ]
  • [ 623-33-6 ]
YieldReaction ConditionsOperation in experiment
90.4% With thionyl chloride In ethanol at -10℃; for 2 h; Heating / reflux 247.3 g of thionyl chloride and 130 g of glycine were introduced into 1000 ml of ethanol at -10° C. After removing the ice bath, a further equivalent of glycine was added portion-wise.The mixture was then stirred under reflux for 2 h. After cooling to room temperature, the excess alcohol and the thionyl chloride were removed using a rotary evaporator.The white solid obtained was treated twice with ethanol, and the latter was in turn removed using the rotary evaporator, in order to completely remove any adhering thionyl chloride. After re-crystallization from ethanol, 218.6 g (90.4percent of theor.) of the title compound (Prod. 2) was obtained.
90.4% With thionyl chloride In ethanol for 2 h; Preparation of Glycine Alkyl Ester Hydrochlorides [GP 1] 1.2 equivalents of thionyl chloride are introduced into 0.6 ml of alcohol per mmol of glycine with ice cooling to -10 C. After removal of the ice bath, 1 equivalent of glycine is added in portions. The mixture is stirred for 2 hours while being refluxed. After cooling to room temperature, the excess alcohol and the thionyl chloride are removed in a rotary evaporator. The resultant white solid is combined twice with the alcohol and the latter is again removed in the rotary evaporator in order to remove any adhering thionyl chloride completely. B) glycine Ethyl Ester Hydrochloride (40)
In accordance with GP 1, 1000 ml of ethanol are reacted with 130 g (1.732 mol) of glycine 39 and 247.3 g (2.08 mol) of thionyl chloride.After recrystallization from ethanol, a colorless, acicular solid is obtained, which is dried under a high vacuum.
1H-NMR spectrum (300 MHz, CD3OD):
δ=4.30 (q, J=7.14, 2H, OCH2), 3.83 (s, 2H, H2CNH2), 1.32 (tr, J=7.14, 3H, CH3) ppm.
13C-NMR spectrum (75 MHz, CD3OD):
δ=167.53 (C=O), 63.46 (OCH2), 41.09 (H2CNH2), 14.39 (CH3) ppm.
All other analytical data are in line with literature values
Reference: [1] Patent: US2003/229145, 2003, A1, . Location in patent: Page 10
[2] Patent: US2003/236429, 2003, A1, . Location in patent: Page 22, 21
[3] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1902, vol. 35, p. 229[4] Chemische Berichte, 1906, vol. 39, p. 589
  • 38
  • [ 77385-90-1 ]
  • [ 623-33-6 ]
Reference: [1] Journal of Organic Chemistry, 2009, vol. 74, # 15, p. 5671 - 5674
  • 39
  • [ 14011-27-9 ]
  • [ 623-33-6 ]
Reference: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1987, vol. 36, p. 1076 - 1077[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1987, vol. 36, # 5, p. 1162 - 1164
  • 40
  • [ 762-04-9 ]
  • [ 623-33-6 ]
Reference: [1] Patent: US4389349, 1983, A,
  • 41
  • [ 626-35-7 ]
  • [ 623-33-6 ]
Reference: [1] Tetrahedron Letters, 1984, vol. 25, # 32, p. 3415 - 3418
  • 42
  • [ 170622-26-1 ]
  • [ 170621-73-5 ]
  • [ 623-33-6 ]
Reference: [1] Patent: US5658933, 1997, A,
  • 43
  • [ 85231-98-7 ]
  • [ 623-33-6 ]
Reference: [1] Synthesis, 1982, # 11, p. 922 - 924
  • 44
  • [ 637-81-0 ]
  • [ 623-33-6 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1985, # 5, p. 815 - 819
  • 45
  • [ 64269-79-0 ]
  • [ 623-33-6 ]
  • [ 121-44-8 ]
Reference: [1] Patent: US5444038, 1995, A,
  • 46
  • [ 64-17-5 ]
  • [ 6000-43-7 ]
  • [ 623-33-6 ]
Reference: [1] Inorganic Chemistry, 2016, vol. 55, # 11, p. 5592 - 5602
  • 47
  • [ 6378-11-6 ]
  • [ 56-40-6 ]
  • [ 623-33-6 ]
Reference: [1] Chemistry and Biodiversity, 2018, vol. 15, # 5,
  • 48
  • [ 7647-01-0 ]
  • [ 1138-80-3 ]
  • [ 1145-81-9 ]
  • [ 623-33-6 ]
Reference: [1] Journal of the American Chemical Society, 1944, vol. 66, p. 951,956
  • 49
  • [ 64-17-5 ]
  • [ 80478-56-4 ]
  • [ 623-33-6 ]
  • [ 6065-82-3 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 1981, vol. 54, # 11, p. 3453 - 3455
[2] Bulletin of the Chemical Society of Japan, 1981, vol. 54, # 11, p. 3453 - 3455
  • 50
  • [ 7647-01-0 ]
  • [ 1138-80-3 ]
  • [ 623-33-6 ]
Reference: [1] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1937, vol. 247, p. 227,234
[2] Journal of the American Chemical Society, 1944, vol. 66, p. 951,956
  • 51
  • [ 64-17-5 ]
  • [ 144232-41-7 ]
  • [ 623-33-6 ]
Reference: [1] Chemische Berichte, 1921, vol. 54, p. 1541
  • 52
  • [ 64-17-5 ]
  • [ 2184-96-5 ]
  • [ 623-33-6 ]
Reference: [1] Chemische Berichte, 1905, vol. 38, p. 2915
  • 53
  • [ 7647-01-0 ]
  • [ 2185-00-4 ]
  • [ 623-33-6 ]
Reference: [1] Chemische Berichte, 1906, vol. 39, p. 858
  • 54
  • [ 861366-27-0 ]
  • [ 7647-01-0 ]
  • [ 623-33-6 ]
Reference: [1] Chemische Berichte, 1923, vol. 56, p. 390
  • 55
  • [ 7647-01-0 ]
  • [ 64-17-5 ]
  • [ 1906-82-7 ]
  • [ 623-33-6 ]
  • [ 141-78-6 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1895, vol. &lt;2&gt;52, p. 440
[2] Chemische Berichte, 1884, vol. 17, p. 1665
  • 56
  • [ 7647-01-0 ]
  • [ 861554-12-3 ]
  • [ 623-33-6 ]
  • [ 123-25-1 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1922, vol. &lt;2&gt;105, p. 302
  • 57
  • [ 623-33-6 ]
  • [ 93-91-4 ]
  • [ 21756-95-6 ]
  • [ 81979-58-0 ]
Reference: [1] Synthesis, 1982, # 2, p. 157 - 159
  • 58
  • [ 623-33-6 ]
  • [ 74-89-5 ]
  • [ 49755-94-4 ]
Reference: [1] Organic and Biomolecular Chemistry, 2010, vol. 8, # 4, p. 864 - 872
[2] Australian Journal of Chemistry, 2012, vol. 65, # 8, p. 1110 - 1116
[3] Tetrahedron Asymmetry, 2011, vol. 22, # 12, p. 1266 - 1273
  • 59
  • [ 623-33-6 ]
  • [ 2087-41-4 ]
  • [ 16194-06-2 ]
Reference: [1] Angewandte Chemie, 1991, vol. 103, # 11, p. 1492 - 1493
  • 60
  • [ 623-33-6 ]
  • [ 123-11-5 ]
  • [ 60857-16-1 ]
YieldReaction ConditionsOperation in experiment
49% With sodium cyanoborohydride In methanol at 20℃; A suspension of glycine ethyl ester hydrochloride (10. 0 G, 71.6 mmol) and NaBH3CN (5.00 g, 79.6 mmol) in MeOH (60 mL) was treated dropwise over 15 min with p-anisaldehyde (11.0 mL, 90.4 mmol). After stirring at room temperature overnight, the solvent was removed in vacuo. The residue was partitioned between CH2CL2 (200 mL) and saturated aqueous NAHC03 (300 mL). The aqueous layer was extracted with CH2C12 (2 x 200 mL) and the combined organic layers were washed with brine, dried over NA2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, hexanes/EtOAc, 90: 10 to 50: 50) gave the title compound (7.77 g, 49percent) as a colorless liquid: MS (ESI) mule 224 (M + H) +.
Reference: [1] Synthesis, 2005, # 19, p. 3412 - 3422
[2] Patent: WO2004/52890, 2004, A1, . Location in patent: Page 50; 100-101
[3] Patent: US2005/26939, 2005, A1, . Location in patent: Page/Page column 4
  • 61
  • [ 623-33-6 ]
  • [ 157115-85-0 ]
Reference: [1] European Journal of Medicinal Chemistry, 1996, vol. 31, # 2, p. 151 - 157
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