* 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.
General procedure: To a stirred solution at -30 °C of 0.1 mol of the appropriate α-acetoxy or α-hydroxy acid in 200 mL of dry methanol, 8.1 mL (13.05 g, 0.11 mol) of thionyl chloride were added slowly. The solution was stirred at -30 °C for further 15 min, and then left for 48 h at room temperature. Then, the solvent was evaporated under reduced pressure. The mixture was alkalized to pH 9 with an NaHCO3 solution, extracted with ethyl ether (5 .x. 50 mL), and dried over MgSO4. After the solvent was evaporated, the resulting crude methyl ester of the α-hydroxycarboxylic acid was purified by distillation under reduced pressure or by crystallization from petroleum ether-toluene mixture.
72%
for 12 h; Reflux
A MeOH (30 mL) solution of (S)-mandelic acid (1.52 g, 10 mmol) and H2SO4 (few drops) was stirred at reflux for 12 h. After the solution was cooled to room temperature, Na2CO3 aq. was added until the pH of the solution was 7. The mixture was extracted with Et2O. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was subjected to silica gel column chromatography to give methyl (S)-mandelate (1.201 g, 7.2 mmol, 72percent yield). Colorless solid; mp 54-55.5 °C; 1H NMR (300 MHz, CDCl3) δ 1.95 (brs, 1H), 3.78 (s, 3H), 5.18 (s, 1H), 7.32-7.44 (m, 5H) ppm; MS (EI) m/z 107, 166 (M+). A THF (20 mL) solution of 2-naphthalenecarboxylic acid (861 mg, 5 mmol), methyl (S)-mandelate (833 mg, 5 mmol), and 4-dimethylaminopyridine (488 mg, 4 mmol) was stirred at 0 °C for 5 min under an argon atmosphere. To the solution was added dicyclohexylcarbodiimide (1.7 mL, 6.6 mmol) at 0 °C, and the solution was stirred at room temperature overnight. The precipitate was removed by filtration. HCl aq. and Et2O were added to the filtrate. The organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was subjected to silica gel column chromatography to give (S)-1-methoxycarbonyl-1-phenylmethyl 2-naphthalenecarboxylate (1d, 1.02 g, 3.2 mmol, 64percent yield). Colorless solid; mp 105.5-107 °C; 1H NMR (300 MHz, CDCl3) δ 3.77 (s, 3H), 6.24 (s, 1H), 7.42-7.65 (m, 7H), 7.86-7.90 (m, 2H), 7.96 (d, J = 8.1 Hz, 1H), 8.12 (dd, J = 7.0, 1.7 Hz, 1H), 8.69 (s, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ 52.8, 75.0, 125.2, 126.3, 126.6, 127.6, 127.7, 128.2, 128.4, 128.8, 129.2, 129.3, 131.5, 131.6, 132.3, 133.9, 135.6, 169.1 ppm; UV (cyclohexane) λmax 281, 292 nm; HRMS (EI) calcd for C15H14O4: 258.0892, found: 258.0880.
Reference:
[1] Patent: JP2005/120020, 2005, A, . Location in patent: Page/Page column 9
[2] Angewandte Chemie, International Edition, 2009, vol. 48, # 25, p. 4605 - 4609
[3] Angewandte Chemie, International Edition, 2014, vol. 53, # 37, p. 9860 - 9864,5[4] Angewandte Chemie, 2014, vol. 126, # 37, p. 10018 - 10022,5
[5] Chemistry Letters, 1997, # 1, p. 55 - 56
[6] Journal of Organic Chemistry, 1987, vol. 52, # 15, p. 3312 - 3316
[7] Tetrahedron Asymmetry, 2011, vol. 22, # 3, p. 294 - 299
[8] Tetrahedron Asymmetry, 1997, vol. 8, # 22, p. 3821 - 3828
[9] Tetrahedron: Asymmetry, 1994, vol. 5, # 9, p. 1763 - 1780
[10] Journal of Organic Chemistry, 1999, vol. 64, # 22, p. 8063 - 8075
[11] Organic Letters, 2008, vol. 10, # 18, p. 3997 - 4000
[12] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1995, # 8, p. 1009 - 1018
[13] Synthetic Communications, 1988, vol. 18, # 8, p. 847 - 854
[14] Agricultural and Biological Chemistry, 1989, vol. 53, # 1, p. 165 - 174
[15] Journal of Chemical Research - Part S, 2000, # 10, p. 488 - 490
[16] Tetrahedron Asymmetry, 1993, vol. 4, # 12, p. 2495 - 2500
[17] Journal of Photochemistry and Photobiology A: Chemistry, 2017, vol. 349, p. 7 - 17
[18] Tetrahedron Asymmetry, 1999, vol. 10, # 19, p. 3701 - 3718
[19] Journal of the Chemical Society, 1936, p. 718,720
[20] Biochemische Zeitschrift, 1927, vol. 181, p. 51
[21] Journal of Organic Chemistry, 1968, vol. 33, # 11, p. 4245 - 4250
[22] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1987, p. 1495 - 1500
[23] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 13, p. 1397 - 1402
[24] Chemische Berichte, 1988, vol. 121, p. 397 - 406
[25] Journal of Organic Chemistry, 1992, vol. 57, # 5, p. 1514 - 1516
[26] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 2, p. 648 - 650
[27] Chemische Berichte, 1994, vol. 127, # 10, p. 1969 - 1980
[28] Tetrahedron Asymmetry, 2005, vol. 16, # 12, p. 2113 - 2117
[29] Tetrahedron, 2006, vol. 62, # 49, p. 11402 - 11412
[30] Tetrahedron Asymmetry, 1991, vol. 2, # 12, p. 1209 - 1221
[31] Journal of the American Chemical Society, 2000, vol. 122, # 24, p. 5897 - 5898
[32] Organic Letters, 2007, vol. 9, # 24, p. 5015 - 5018
[33] Patent: EP1538148, 2005, A1, . Location in patent: Page/Page column 9
[34] Tetrahedron Asymmetry, 2009, vol. 20, # 3, p. 351 - 354
[35] Synthetic Communications, 2009, vol. 39, # 18, p. 3217 - 3231
[36] Chemical Communications, 2011, vol. 47, # 38, p. 10608 - 10610
[37] Angewandte Chemie - International Edition, 2012, vol. 51, # 31, p. 7825 - 7829
2
[ 15206-55-0 ]
[ 21210-43-5 ]
Yield
Reaction Conditions
Operation in experiment
80 % ee
With hydrogen In toluene at 20℃; for 1 - 1.16667 h;
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
90 % ee
With hydrogen In toluene at 20℃; for 1 - 1.16667 h;
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
91.5 % ee
With hydrogen In methanol at 50℃; for 24 h;
The substrate to be hydrogenated (1 mmol) is then dissolved in 2 ml of hydrogenation solvent (of the alcohol or halogenated type, such as dichloromethane) and placed in an autoclave in the presence of the catalyst under the desired hydrogen pressure and at the desired temperature.
80 % ee
With hydrogen In toluene for 1 - 1.16667 h;
Examples B13 - B24: Hydrogenation of methyl phenylketoacetate[0052] The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
90 % ee
With hydrogen In toluene for 1 - 1.16667 h;
Examples B13 - B24: Hydrogenation of methyl phenylketoacetate[0052] The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
100 %Chromat.
With D-glucose In aq. phosphate buffer; ethanol at 37℃; Enzymatic reaction
General procedure: For a typical experiment, 0.14 g glucose (7.6 × 10-4 mol) was added to a suspension of Boni Protect (2 g) in 30 mL of potassium phosphate buffer (pH 7.0) and the resulting suspension was stirred at 37 °C for 30 min. Then an additive compound (1.25 ×10-5 mol; see Table 2) and substrate (1.25 × 10-4 mol in 0.5 mL EtOH) were added and stirring was continued at the same temperature. The reaction progress was monitored by TLC (the solvent system used was hexane:ethyl acetate 3:1). After the reaction, hyflo-super celit and ethyl acetate were added and the mixture was filtered. The celit was washed with ethyl acetate and combined filtrates were extracted with ethyl acetate (5 × 20 mL). The organic portion was dried with MgSO4. The solvent was evaporated under reduced pressure. The crude product was purified by PLC (Preparative Layer Plate) using hexane:ethyl acetate (3:1) as eluent. The enantiomeric ratios were determined on an HPLC system using a chiral column.
Reference:
[1] Journal of Organic Chemistry, 1992, vol. 57, # 5, p. 1526 - 1532
[2] Angewandte Chemie - International Edition in English, 1997, vol. 36, # 11, p. 1207 - 1211
[3] Journal of the American Chemical Society, 2000, vol. 122, # 19, p. 4563 - 4568
[4] Journal of the Chemical Society, Chemical Communications, 1992, # 12, p. 905 - 906
[5] Tetrahedron Letters, 1993, vol. 34, # 14, p. 2351 - 2354
[6] Journal of the American Chemical Society, 1979, vol. 101, p. 7036 - 7040
[7] Tetrahedron Letters, 1993, vol. 34, # 14, p. 2351 - 2354
[8] Journal of the American Chemical Society, 2006, vol. 128, # 17, p. 5955 - 5965
[9] Journal of Organic Chemistry, 2008, vol. 73, # 3, p. 1143 - 1146
[10] Journal of Organic Chemistry, 2008, vol. 73, # 15, p. 6003 - 6005
[11] Journal of Organic Chemistry, 2009, vol. 74, # 17, p. 6691 - 6702
[12] Tetrahedron Asymmetry, 2009, vol. 20, # 17, p. 2033 - 2037
[13] Patent: US2003/204112, 2003, A1, . Location in patent: Page/Page column 7
[14] Patent: US2003/204112, 2003, A1, . Location in patent: Page/Page column 7
[15] Patent: US2004/260101, 2004, A1, . Location in patent: Page 10-11
[16] Patent: EP1354883, 2003, A1, . Location in patent: Page/Page column 11
[17] Patent: EP1354883, 2003, A1, . Location in patent: Page/Page column 11
[18] Organic and Biomolecular Chemistry, 2011, vol. 9, # 11, p. 4070 - 4078
[19] Organic and Biomolecular Chemistry, 2014, vol. 12, # 4, p. 673 - 681
[20] Catalysis Communications, 2017, vol. 101, p. 81 - 84
3
[ 15206-55-0 ]
[ 21210-43-5 ]
[ 20698-91-3 ]
Yield
Reaction Conditions
Operation in experiment
59.2 % ee
With hydrogen In toluene at 25℃; for 20 h;
The experimental procedure is similar to that of Example DI. 2.53 mmol of starting material are always used, and the ratio of substrate to catalyst (sic) is always 200. The reaction parameters and the results are summarized in Table I below.In Examples 5, 11, 16 and 20, toluene (10 ml) is used as solvent. In Examples 6 to 8, 12, 13, 17, 18, 21 and 22, ethanol (10 ml, in Examples 6 and 17 9.5 ml) is used as solvent. In Examples 9, 10, 14, 15 and 19, methanol (10 ml) is used as solvent.
18 % ee
With hydrogen In acetic acid at 20℃; for 1 - 1.16667 h;
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
78 % ee
With hydrogen In toluene at 20℃; for 1 - 1.16667 h;
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
51 % ee
With hydrogen In acetic acid at 20℃; for 1 - 1.16667 h;
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
31 % ee
With hydrogen In toluene at 20℃; for 1 - 1.16667 h;
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
8 % ee
With hydrogen In toluene at 20℃; for 1 - 1.16667 h;
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
Reference:
[1] Chemical Communications, 2007, # 18, p. 1825 - 1827
[2] Tetrahedron Letters, 1996, vol. 37, # 19, p. 3275 - 3278
[3] Tetrahedron, 2010, vol. 66, # 17, p. 3187 - 3194
[4] Tetrahedron, 1989, vol. 45, # 3, p. 733 - 740
[5] Tetrahedron, 1989, vol. 45, # 3, p. 733 - 740
[6] Tetrahedron, 1991, vol. 47, # 3, p. 429 - 440
[7] Journal of Heterocyclic Chemistry, 1989, vol. 26, # 6, p. 1595 - 1600
[8] Tetrahedron, 1991, vol. 47, # 45, p. 9369 - 9382
[9] Tetrahedron, 1993, vol. 49, # 26, p. 5831 - 5844
[10] Tetrahedron, 1993, vol. 49, # 24, p. 5237 - 5246
[11] Tetrahedron: Asymmetry, 1993, vol. 4, # 7, p. 1635 - 1644
[12] Journal of the Chemical Society, Chemical Communications, 1985, # 17, p. 1162 - 1163
[13] Tetrahedron, 1995, vol. 51, # 23, p. 6459 - 6474
[14] Tetrahedron Letters, 1995, vol. 36, # 36, p. 6491 - 6494
[15] Chemistry Letters, 1996, # 5, p. 359 - 360
[16] Chemical Communications, 1996, # 22, p. 2535 - 2536
[17] Angewandte Chemie - International Edition in English, 1997, vol. 36, # 11, p. 1207 - 1211
[18] Heterocycles, 1997, vol. 45, # 8, p. 1441 - 1446
[19] Journal of Organic Chemistry, 1989, vol. 54, # 7, p. 1577 - 1583
[20] Journal of Organic Chemistry, 1990, vol. 55, # 26, p. 6328 - 6333
[21] Tetrahedron, 1991, vol. 47, # 3, p. 429 - 440
[22] Journal of Organic Chemistry, 1988, vol. 53, # 6, p. 1231 - 1238
[23] Chemistry Letters, 1985, p. 813 - 816
[24] Journal of the American Chemical Society, 1985, vol. 107, p. 3981
[25] Journal of the American Chemical Society, 1988, vol. 110, # 5, p. 1539 - 1546
[26] Tetrahedron, 1993, vol. 49, # 35, p. 7793 - 7802
[27] Tetrahedron: Asymmetry, 1992, vol. 3, # 1, p. 73 - 84
[28] Journal of the Chemical Society, Chemical Communications, 1992, # 6, p. 494 - 496
[29] Tetrahedron Letters, 1991, vol. 32, # 46, p. 6691 - 6694
[30] Tetrahedron: Asymmetry, 1994, vol. 5, # 4, p. 675 - 690
[31] Journal of Organic Chemistry, 1994, vol. 59, # 11, p. 3064 - 3076
[32] Journal of the Chemical Society, Chemical Communications, 1995, # 6, p. 685 - 686
[33] Tetrahedron, 1995, vol. 51, # 23, p. 6459 - 6474
[34] Tetrahedron, 1995, vol. 51, # 23, p. 6459 - 6474
[35] Journal of Organic Chemistry, 1996, vol. 61, # 18, p. 6244 - 6251
[36] Tetrahedron Asymmetry, 1997, vol. 8, # 19, p. 3309 - 3318
[37] Heterocycles, 1997, vol. 45, # 8, p. 1441 - 1446
[38] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1990, # 6, p. 1826 - 1828
[39] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1989, p. 867 - 872
[40] Journal of Organic Chemistry, 1990, vol. 55, # 26, p. 6328 - 6333
[41] Chemistry Letters, 1991, # 1, p. 125 - 128
[42] Journal of Organic Chemistry, 1986, vol. 51, # 17, p. 3396 - 3398
[43] Journal of Organic Chemistry, 1987, vol. 52, # 24, p. 5406 - 5412
[44] Journal of Organic Chemistry, 1985, vol. 50, # 9, p. 1384 - 1394
[45] Journal of the American Chemical Society, 1984, vol. 106, # 5, p. 1531 - 1533
[46] Tetrahedron, 1993, vol. 49, # 35, p. 7793 - 7802
[47] Tetrahedron, 1991, vol. 47, # 45, p. 9369 - 9382
[48] Tetrahedron: Asymmetry, 1994, vol. 5, # 4, p. 675 - 690
[49] Journal of Organic Chemistry, 1994, vol. 59, # 11, p. 3064 - 3076
[50] Chemistry Letters, 1996, # 5, p. 359 - 360
[51] Chemical Communications, 1996, # 22, p. 2535 - 2536
[52] Tetrahedron, 1998, vol. 54, # 5-6, p. 705 - 714
[53] Tetrahedron Letters, 1999, vol. 40, # 13, p. 2577 - 2580
[54] Tetrahedron Asymmetry, 1999, vol. 10, # 9, p. 1813 - 1819
[55] Tetrahedron Asymmetry, 2000, vol. 11, # 14, p. 3027 - 3040
[56] Journal of Organic Chemistry, 2000, vol. 65, # 24, p. 8340 - 8347
[57] Tetrahedron, 2001, vol. 57, # 15, p. 3087 - 3098
[58] Tetrahedron Letters, 2001, vol. 42, # 28, p. 4613 - 4616
[59] Tetrahedron Letters, 2001, vol. 42, # 22, p. 3713 - 3716
[60] Advanced Synthesis and Catalysis, 2001, vol. 343, # 3, p. 289 - 298
[61] Tetrahedron, 2001, vol. 57, # 44, p. 9101 - 9108
[62] Journal of Organic Chemistry, 2002, vol. 67, # 15, p. 5315 - 5319
[63] Tetrahedron Asymmetry, 2002, vol. 13, # 13, p. 1379 - 1384
[64] Chemical communications (Cambridge, England), 2002, # 19, p. 2256 - 2257
[65] Chemical communications (Cambridge, England), 2002, # 19, p. 2256 - 2257
[66] Tetrahedron Asymmetry, 2002, vol. 13, # 23, p. 2605 - 2608
[67] Tetrahedron, 2003, vol. 59, # 24, p. 4303 - 4308
[68] European Journal of Organic Chemistry, 2003, # 10, p. 1931 - 1941
[69] Advanced Synthesis and Catalysis, 2003, vol. 345, # 11, p. 1253 - 1260
[70] Journal of the American Chemical Society, 2003, vol. 125, # 49, p. 14982 - 14983
[71] Journal of Catalysis, 2004, vol. 224, # 2, p. 463 - 472
[72] Tetrahedron Asymmetry, 2004, vol. 15, # 14, p. 2253 - 2261
[73] Tetrahedron Asymmetry, 2004, vol. 15, # 14, p. 2299 - 2306
[74] Tetrahedron Asymmetry, 2004, vol. 15, # 14, p. 2307 - 2311
[75] Synlett, 2005, # 3, p. 441 - 444
[76] Tetrahedron Asymmetry, 2005, vol. 16, # 15, p. 2525 - 2530
[77] Tetrahedron Asymmetry, 2005, vol. 16, # 15, p. 2525 - 2530
[78] Tetrahedron Asymmetry, 2006, vol. 17, # 12, p. 1769 - 1774
[79] Organic Letters, 2006, vol. 8, # 10, p. 2067 - 2070
[80] Canadian Journal of Chemistry, 2005, vol. 83, # 6-7, p. 903 - 908
[81] Organic Letters, 2006, vol. 8, # 24, p. 5653 - 5655
[82] Chemical communications (Cambridge, England), 2002, # 19, p. 2256 - 2257
[83] Molecules, 2007, vol. 12, # 3, p. 415 - 422
[84] Synlett, 2006, # 8, p. 1169 - 1172
[85] Molecules, 2007, vol. 12, # 5, p. 979 - 987
[86] Tetrahedron Asymmetry, 2007, vol. 18, # 19, p. 2305 - 2312
[87] Tetrahedron Asymmetry, 2007, vol. 18, # 21, p. 2537 - 2540
[88] Tetrahedron Asymmetry, 2008, vol. 19, # 16, p. 1954 - 1958
[89] Patent: US2008/287698, 2008, A1, . Location in patent: Page/Page column 15
[90] Organic Letters, 2008, vol. 10, # 11, p. 2155 - 2158
[91] Journal of Organic Chemistry, 2009, vol. 74, # 12, p. 4608 - 4611
[92] Journal of Catalysis, 2008, vol. 260, # 2, p. 245 - 253
[93] Journal of Catalysis, 2008, vol. 260, # 2, p. 245 - 253
[94] Journal of Organic Chemistry, 2009, vol. 74, # 17, p. 6691 - 6702
[95] Tetrahedron Asymmetry, 2009, vol. 20, # 17, p. 2033 - 2037
[96] Patent: US2003/204112, 2003, A1, . Location in patent: Page/Page column 7
[97] Patent: US2003/204112, 2003, A1, . Location in patent: Page/Page column 7
[98] Patent: US2003/204112, 2003, A1, . Location in patent: Page/Page column 7
[99] Patent: US2003/204112, 2003, A1, . Location in patent: Page/Page column 7
[100] Patent: US2003/204112, 2003, A1, . Location in patent: Page/Page column 7
4
[ 22979-35-7 ]
[ 21210-43-5 ]
[ 20698-91-3 ]
Reference:
[1] Angewandte Chemie - International Edition, 2008, vol. 47, # 5, p. 932 - 934
[2] Chemical and Pharmaceutical Bulletin, 2010, vol. 58, # 6, p. 872 - 874
[3] Chemical and Pharmaceutical Bulletin, 2010, vol. 58, # 6, p. 872 - 874
[4] Angewandte Chemie - International Edition, 2014, vol. 53, # 11, p. 2978 - 2981[5] Angew. Chem., 2014, # 11, p. 3022 - 3025,4
5
[ 4358-87-6 ]
[ 15206-55-0 ]
[ 21210-43-5 ]
[ 20698-91-3 ]
Reference:
[1] Advanced Synthesis and Catalysis, 2011, vol. 353, # 8, p. 1234 - 1240
[2] Chemical Communications, 2010, vol. 46, # 38, p. 7235 - 7237
[3] Advanced Synthesis and Catalysis, 2008, vol. 350, # 17, p. 2823 - 2834
6
[ 4358-87-6 ]
[ 21210-43-5 ]
[ 20698-91-3 ]
Reference:
[1] Analytical Chemistry, 2003, vol. 75, # 6, p. 1348 - 1354
[2] Patent: EP907663, 2004, B1, . Location in patent: Page 11
[3] Patent: US2008/234525, 2008, A1, . Location in patent: Page/Page column 9
[4] Chirality, 2010, vol. 22, # 5, p. 479 - 485
[5] Chirality, 2012, vol. 24, # 4, p. 329 - 338
[6] Asian Journal of Chemistry, 2012, vol. 24, # 11, p. 4917 - 4922
[7] Bulletin of the Korean Chemical Society, 2013, vol. 34, # 9, p. 2623 - 2628
[8] ChemPlusChem, 2013, vol. 78, # 12, p. 1466 - 1474
[9] Journal of the American Chemical Society, 2016, vol. 138, # 3, p. 1046 - 1056
7
[ 67-56-1 ]
[ 119072-55-8 ]
[ 100-52-7 ]
[ 21210-43-5 ]
Reference:
[1] Journal of Organic Chemistry, 2005, vol. 70, # 24, p. 9667 - 9676
8
[ 17199-29-0 ]
[ 77-76-9 ]
[ 21210-43-5 ]
Reference:
[1] Journal of the American Chemical Society, 1986, vol. 108, # 19, p. 6024 - 6031
[2] Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 8, p. 1957 - 1968
Reference:
[1] Journal of the American Chemical Society, 1987, vol. 109, # 10, p. 3155 - 3156
17
[ 13049-41-7 ]
[ 21210-43-5 ]
[ 20698-91-3 ]
Reference:
[1] Chemistry Letters, 1986, p. 131 - 134
[2] Chemistry - A European Journal, 1999, vol. 5, # 8, p. 2270 - 2280
18
[ 67-56-1 ]
[ 13704-09-1 ]
[ 21210-43-5 ]
Reference:
[1] Synlett, 2007, # 3, p. 491 - 493
19
[ 25726-04-9 ]
[ 21210-43-5 ]
Reference:
[1] Journal of the American Chemical Society, 1987, vol. 109, # 10, p. 3155 - 3156
[2] Journal of the American Chemical Society, 1987, vol. 109, # 10, p. 3155 - 3156
Reference:
[1] Journal of the American Chemical Society, 2006, vol. 128, # 18, p. 6058 - 6059
[2] Tetrahedron Asymmetry, 2007, vol. 18, # 21, p. 2537 - 2540
33
[ 611-71-2 ]
[ 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
1.1 The synthetic method of compound (I) (S)-2-hydroxy-1-(2-iminothiazolin-3-yl)-2-phenylethan-1-one, the concrete steps are:
In the reaction flask, add 100.0g L-mandelic acid,300.0g methanol,1.1g sulfuric acid,The temperature was raised to 65 °C, the reaction was refluxed for 2 h, and the solvent was removed under reduced pressure.Add 150g toluene,Sodium bicarbonate solution (1.8g sodium bicarbonate dissolved in 50g water),Separation, the toluene phase was washed once with 50 g of water,Toluene was removed under reduced pressure to obtain a colorless liquid,After cooling to room temperature, it turned into a white solid.Methyl L-mandelate, 108.1 g, yield 99%;
98.6%
for 2h; Heating / reflux;
97%
With toluene-4-sulfonic acid for 3h; Inert atmosphere; Reflux;
97%
With toluene-4-sulfonic acid In lithium hydroxide monohydrate for 3h; Reflux;
96%
With ethenetetracarbonitrile for 48h; Ambient temperature;
96%
With toluene-4-sulfonic acid In dichloromethane for 24h; Heating;
95.5%
With aminosulfonic acid at 60℃;
1.1; 2.1; 3.1
(1) Take 100g of S-mandelic acid, add it to 500ml of methanol, then add 20g of sulfamic acid catalyst, and warm upCatalyze the reflux at 60°C, and check the reaction status by TLC. After the reaction is completed, the catalyst is filtered off and recovered. The filtrate is 55-60°CConcentrate and recover the solvent. After concentrating until no solvent is distilled off, add 200ml of water to crystallize for 1h. After the crystallization is completed, filter to obtain S-flatMethyl peachate 104.2g, purity 99.24%, yield 95.5%.
94%
With thionyl chloride at -30 - 20℃; for 48.25h;
4.4. Preparation of optically active (S)-α-hydroxycarboxylic acid methyl esters 3b-f
General procedure: To a stirred solution at -30 °C of 0.1 mol of the appropriate α-acetoxy or α-hydroxy acid in 200 mL of dry methanol, 8.1 mL (13.05 g, 0.11 mol) of thionyl chloride were added slowly. The solution was stirred at -30 °C for further 15 min, and then left for 48 h at room temperature. Then, the solvent was evaporated under reduced pressure. The mixture was alkalized to pH 9 with an NaHCO3 solution, extracted with ethyl ether (5 × 50 mL), and dried over MgSO4. After the solvent was evaporated, the resulting crude methyl ester of the α-hydroxycarboxylic acid was purified by distillation under reduced pressure or by crystallization from petroleum ether-toluene mixture.
92%
With acetyl chloride for 2h; Ambient temperature;
91%
With toluene-4-sulfonic acid In Carbon tetrachloride Heating;
90%
With thionyl chloride for 4h; Heating;
90%
With sulfuric acid; 2,2-dimethoxy-propane Reflux;
88%
With sulfuric acid for 24h; Heating;
88%
With sulfuric acid In lithium hydroxide monohydrate for 4h; Reflux; Inert atmosphere;
88%
With sulfuric acid for 4h; Reflux;
1 (S)-(+)-Mandelic acid methyl ester (1)
To a solution of (S)-(+)-Mandelic acid (57.13 g, 376 mmol, 1 eq) in MeOH (300 mL), concentrated sulfuric acid (600 µL, 11.3 mmol, 0.03 eq) was added and the mixture was refluxed for 4 h. The reaction was quenched with K2CO3 (1.04 g, 7.52 mmol, 0.02 eq) in 1.2 mL of water and the MeOH was evapo- rated in vacuo. Then Et2O (300 mL) was added and the solid was filtered off; the mixture was concentrated and crystallized from hexane (75 mL) to furnish ester 1 (54.9 g, 330.72 mmol, 88%) as a white solid. General Data: C9H10O3; FW: 166.06; Mp: 56-58°C; TLC: Rf= 0.35 (Pen- tane/Et2O 1:1); UV (+); Vanillin: yellow. 1H-NMR (600 MHz, CDCl3): δ (ppm): 7.36-7.34 (d, 2H); 7.31-7.30 (d, 2H); 7.27-7.26 (dd, 1H); 5.11 (s, 1H), 3.69 (s, 3H). 13C-NMR (151 MHz, CDCl3): δ (ppm): 174.17; 138.22; 128.65; 128.55; 126.65; 126.61; 72.89 (C-2); 53.09.
87%
In methanol for 6h; Ambient temperature;
87%
Stage #1: methanol; (S)-Mandelic acid With thionyl chloride for 0.166667h; Schlenk technique; Inert atmosphere; Cooling with ice;
Stage #2: With thionyl chloride at 0 - 75℃; Schlenk technique; Inert atmosphere;
80%
With sulfuric acid for 8h; Heating;
80%
With toluene-4-sulfonic acid for 10h;
77%
With chloro-trimethyl-silane for 24h; Ambient temperature;
72%
With sulfuric acid for 12h; Reflux;
5 4.5 Preparation of (S)-1-methoxycarbonyl-1-phenylmethyl 2-naphthalenecarboxylate (1d)
A MeOH (30 mL) solution of (S)-mandelic acid (1.52 g, 10 mmol) and H2SO4 (few drops) was stirred at reflux for 12 h. After the solution was cooled to room temperature, Na2CO3 aq. was added until the pH of the solution was 7. The mixture was extracted with Et2O. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was subjected to silica gel column chromatography to give methyl (S)-mandelate (1.201 g, 7.2 mmol, 72% yield). Colorless solid; mp 54-55.5 °C; 1H NMR (300 MHz, CDCl3) δ 1.95 (brs, 1H), 3.78 (s, 3H), 5.18 (s, 1H), 7.32-7.44 (m, 5H) ppm; MS (EI) m/z 107, 166 (M+). A THF (20 mL) solution of 2-naphthalenecarboxylic acid (861 mg, 5 mmol), methyl (S)-mandelate (833 mg, 5 mmol), and 4-dimethylaminopyridine (488 mg, 4 mmol) was stirred at 0 °C for 5 min under an argon atmosphere. To the solution was added dicyclohexylcarbodiimide (1.7 mL, 6.6 mmol) at 0 °C, and the solution was stirred at room temperature overnight. The precipitate was removed by filtration. HCl aq. and Et2O were added to the filtrate. The organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was subjected to silica gel column chromatography to give (S)-1-methoxycarbonyl-1-phenylmethyl 2-naphthalenecarboxylate (1d, 1.02 g, 3.2 mmol, 64% yield). Colorless solid; mp 105.5-107 °C; 1H NMR (300 MHz, CDCl3) δ 3.77 (s, 3H), 6.24 (s, 1H), 7.42-7.65 (m, 7H), 7.86-7.90 (m, 2H), 7.96 (d, J = 8.1 Hz, 1H), 8.12 (dd, J = 7.0, 1.7 Hz, 1H), 8.69 (s, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ 52.8, 75.0, 125.2, 126.3, 126.6, 127.6, 127.7, 128.2, 128.4, 128.8, 129.2, 129.3, 131.5, 131.6, 132.3, 133.9, 135.6, 169.1 ppm; UV (cyclohexane) λmax 281, 292 nm; HRMS (EI) calcd for C15H14O4: 258.0892, found: 258.0880.
55%
With sulfuric acid In benzene Heating;
With sulfuric acid
With hydrogenchloride
With hydrogenchloride
With hydrogenchloride for 1h; Heating;
With hydrogenchloride
With sulfuric acid for 5h; Heating;
acid-catalyzed;
With hydrogen cation
With acetyl chloride Yield given;
With chloro-trimethyl-silane
With acetyl chloride at 20℃; for 24h;
With hydrogenchloride for 2h; Ambient temperature; Yield given;
With sulfuric acid; 2,2-dimethoxy-propane
With thionyl chloride at 20℃; for 24h;
With thionyl chloride at 0 - 20℃; for 23h;
1
Example 1 [Preparation of Chiral Unit (S)-4] A 1-L three-neck flask was charged with methanol (300 mL, 7.41 mol) and (S)-(+)-mandelic acid 5 (50.2 g, 330 mmol) while stirring, and the mixture was cooled to 0°C in an ice-salt bath. Thereafter, thionyl chloride (27.0 mL, 379 mmol) was gradually added dropwise thereto from a dropping funnel. After the termination of the dropwise addition, the temperature of the mixture was recovered to an ambient temperature, at which the mixture was stirred for 23 hours. Next, excess thionyl chloride and methanol were distillated under reduced pressure. Thereafter, the residue was extracted with chloroform, and an organic layer was washed with water and with saturated brine, and the mixture obtained was dried over anhydrous magnesium sulfate, and thereafter concentrated, thereby giving methyl (S)-(+)-mandelate (S)-6 (47.5 g, 286 mmol) in the form of a white solid. A 1-L eggplant-shaped flask equipped with a calcium chloride tube was charged with chloroform (700 mL) and methyl (S)-(+)-mandelate (S)-6 (47.3 g, 285 mmol), and thereafter dihydropyran (100 mL, 1.07 mol) was added thereto, while stirring for 40 minutes in an ice bath, and pyridinium p-toluenesulfonate (3.56 g, 14.2 mmol) was added thereto. The temperature of the mixture was recovered to room temperature, and the mixture was stirred for 3 hours. Thereafter, the mixture was washed with water and with saturated brine, and the mixture obtained was dried over anhydrous magnesium sulfate and concentrated, to give an yellowish oily crude product (S)-7 (93.9 g). A 1-L three-neck flask was charged with anhydrous tetrahydrofuran (500 mL) under nitrogen gas stream, and the content was cooled to -20°C in a dry ice-oil bath. Thereafter, lithium aluminum hydride (6.92 g, 182 mmol) was gradually added thereto. Next, a solution prepared by dissolving the yellowish oily crude product (S)-7 (32.9 g) in anhydrous tetrahydrofuran (50 mL) was gradually added dropwise to the above-mentioned solution over a period of 1 hour, and the mixture was stirred at room temperature for 3 hours. Thereafter, the mixture obtained was again cooled to -20°C in the dry ice-oil bath, and acetone (45 mL) was added thereto to stop the reaction. After the solution was stirred overnight, this solution was subjected to suction filtration, and each of a solid portion and a filtrate portion was extracted with hexane-ethyl acetate. The organic layer was washed with saturated brine. Thereafter, the mixture obtained was dried over anhydrous magnesium sulfate, and concentrated, to give (S)-4 (24.9 g, 112 mmol) in the form of a pale yellowish oily product (yield: 97%).
General procedure: To an ice-cooled solution of the appropriate alpha-hydroxycarboxylic acid methyl ester 3a-f (20 mmol) in anhydrous ethyl ether (360 mL), LiAlH4 (0.759 g, 20 mmol) was slowly added. The resulting mixture was stirred at 0 C for 1 h and then at room temperature for 3 h. The content of the flask was again cooled to 0 C, and after the addition of a THF/H2O (1:1) mixture (4 mL) was stirred overnight at room temperature. The precipitate formed was filtered off, and dissolved in 18% hydrochloric acid solution. The resulting solution was extracted with ethyl acetate (6 × 40 mL) and the combined organic layers were washed with saturated Na2CO3 solution, dried over anhydrous Na2SO4, and evaporated to dryness. The product was purified by distillation or recrystallization from ethyl ether-hexane mixture.
With NAD; isopropyl alcohol In hexane; water Ambient temperature; PED alcohol dehydrogenase, phosphate buffer pH 7.1;
63%
With magnesium(II) perchlorate; (R,S)-<10>(2,5)pyridinophane-1-methyl-1,4-dihydro-3-(1-hydroxymethylisopropylcarbamoyl) In acetonitrile at 75℃; for 6h;
63%
With magnesium(II) perchlorate; [(R)-(2,5-(CH2)10-1-Me-1,4-dihydronicotinoyl)]-(S)-valinol In acetonitrile at 75℃; for 6h;
28%
With magnesium(II) perchlorate; (-)-1-methyl-2-(2'-methoxy-1'-naphthyl)-N,N-diethyl-1,4-dihydronicotinamide In acetonitrile for 72h; Ambient temperature;
With hydrogen In ethanol at 25℃; other carbonyl compounds; other Ru(II)-catalysts; other solvents and H2-pressures; enantioselectivity;
With magnesium(II) perchlorate; (4S,9R)-(+)-N-α-methylbenzyl-1-propyl-2,4-dimethyl-3-carbamoyl-1,4-dihydropyridine In acetonitrile
With hydrogen In ethanol at 25℃;
With hydrogen In methanol at 20℃; for 20h;
With hydrogen In methanol; N,N-dimethyl-formamide at 20℃; for 20h;
With glucose dehydrogenase; D-glucose In various solvent(s) at 30℃; for 24h;
100 %Spectr.
With magnesium(II) perchlorate; (3R)-3-[(5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-1-[bis(trimethylsilyl)methyl]-3-(N-methyl-dihydronicotinamido)-azetidin-2-one In [D3]acetonitrile at 20℃; for 14h; Inert atmosphere; Darkness; optical yield given as %ee;
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; sodium formate; dodecyltrimethylammonium bromide; (-)-(1S,2S)-N-(2,4,6-triisopropybenzenesulfonyl)-1,2-diphenylethylenediamine In water at 28℃; for 1.5h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;
80 % ee
With hydrogen In toluene at 20℃; for 1 - 1.16667h;
B21
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
90 % ee
With hydrogen In toluene at 20℃; for 1 - 1.16667h;
B24
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
91.5 % ee
With hydrogen In methanol at 50℃; for 24h;
6.a
The substrate to be hydrogenated (1 mmol) is then dissolved in 2 ml of hydrogenation solvent (of the alcohol or halogenated type, such as dichloromethane) and placed in an autoclave in the presence of the catalyst under the desired hydrogen pressure and at the desired temperature.
80 % ee
With hydrogen In toluene for 1 - 1.16667h;
B21
Examples B13 - B24: Hydrogenation of methyl phenylketoacetate[0052] The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
90 % ee
With hydrogen In toluene for 1 - 1.16667h;
B24
Examples B13 - B24: Hydrogenation of methyl phenylketoacetate[0052] The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
With recombinant stereospecific carbonyl reductase 1 from Candida parapsilosis; NAD In aq. phosphate buffer at 30℃; for 6h;
> 99 % ee
With alcohol dehydrogenase from Lactobacillus brevis; isopropyl alcohol In aq. phosphate buffer at 30℃; for 48h; Enzymatic reaction; enantioselective reaction;
100 %Chromat.
With D-glucose In aq. phosphate buffer; ethanol at 37℃; Enzymatic reaction; enantioselective reaction;
2.1. Asymmetric reduction by Aureobasidium pullulans
General procedure: For a typical experiment, 0.14 g glucose (7.6 × 10-4 mol) was added to a suspension of Boni Protect (2 g) in 30 mL of potassium phosphate buffer (pH 7.0) and the resulting suspension was stirred at 37 °C for 30 min. Then an additive compound (1.25 ×10-5 mol; see Table 2) and substrate (1.25 × 10-4 mol in 0.5 mL EtOH) were added and stirring was continued at the same temperature. The reaction progress was monitored by TLC (the solvent system used was hexane:ethyl acetate 3:1). After the reaction, hyflo-super celit and ethyl acetate were added and the mixture was filtered. The celit was washed with ethyl acetate and combined filtrates were extracted with ethyl acetate (5 × 20 mL). The organic portion was dried with MgSO4. The solvent was evaporated under reduced pressure. The crude product was purified by PLC (Preparative Layer Plate) using hexane:ethyl acetate (3:1) as eluent. The enantiomeric ratios were determined on an HPLC system using a chiral column.
99 % ee
With Arthrobacter sp. TS-15 recombinant pseudoephedrine dehydrogenase; NADH In aq. phosphate buffer at 25℃; Green chemistry; Enzymatic reaction; enantioselective reaction;
94 % ee
With alcohol dehydrogenase P2-D03; isopropyl alcohol; NADPH In aq. phosphate buffer at 30℃; for 24h; Enzymatic reaction; enantioselective reaction;
With formic acid*triethylamine In isopropyl alcohol at 20℃; for 12h;
83%
With magnesium(II) perchlorate; (4S,9S)-2,6-dimethyl-3-ethoxylcarbonyl-5-(N-α-methylbenzylcarbamoyl)-1-N-propyl-4-<(2S)-pinyl>-1,4-dihydro-pyridine In acetonitrile at 61℃; for 480h; Yields of byproduct given;
70%
With magnesium(II) perchlorate; (3R)-3-benzyl-1-(tert-butyl)-3-(N-methyl-1,4-dihydronicotinamido)azetidin-2-one In [D3]acetonitrile at 26.84℃; for 16h; Darkness; optical yield given as %ee; enantioselective reaction;
68%
With magnesium(II) perchlorate; chiral Hantzsch ester In acetonitrile at 70℃; for 60h;
66%
With magnesium(II) perchlorate; chiral Hantzsch ester In acetonitrile at 70℃; for 480h;
With magnesium(II) perchlorate; 1-(phenyl-2-ethyl)-7-methyl-3,5-N,N-bis-[(S)-(1-benzylhydroxyethyl)aminocarbonyl]-4,7-dihydropyrrolo[2,3-b]pyridine In acetonitrile at 60℃; for 12h; dependence of enantiomeric excess on mol ratio of substrate and reductant;
With magnesium(II) perchlorate; N,N'-3,5-((S)-1-hydroxymethyl-2-phenylethyl)dicarboxamide-7-methyl-4,7-dihydrothieno<2,3-b>pyridine In acetonitrile at 60℃; for 48h; other chiral reagents, stereoselectivity;
With 1-methyl-6-<(S)-1-benzylhydroxyethyl>-1,4,5,6,7,8-hexahydro-5-oxo-1,6-naphthyridine In acetonitrile at 20℃; for 72h; other temperatures, other reaction times, other NADH models as reagents;
With 2,6-di<N-(S)-(1-hydroxymethyl-2-phenylethyl)>aminocarbonyl-1-methyl-4,7-dihydropyrrolo<3,2-b>pyridine; magnesium(II) In acetonitrile at 60℃; for 24h; other chiral NADH model compound, other conditions, enantioselectivity;
With magnesium(II) perchlorate; NADH model 3 In acetonitrile at 0℃; for 0.25h; other temperatures, other NADH models, enantioselectivity;
With (S)-1-methyl-5-oxo-6-<1-(hydroxymethyl)-2-phenylethyl)-1,4,5,6,7,8-hexahydro-1,6-naphtyridine (1a); magnesium ions var. chiral auxiliary amino alcohols;
With 2,6-dimethyl-3,5-dimethoxycarbonyl-1,4-dihydropyridine In acetonitrile at 70℃; for 72h; other reductor, chiral catalysts, solvents, temperatures, times;
With 1-benzyl-3-N-(3-deoxy-1,2-O-isopropylidene-α-D-glucofuranos-3-yl)carbamoyl-1,4-dihydropyridine; Mg(ClO)4 In acetonitrile for 168h; Ambient temperature; enantioselectivity examined; sev. diacetone-D-glucoses, var time;
With magnesium(II) perchlorate; <i>N</i>-<i>tert</i>-butoxycarbonyl-<i>L</i>-phenylalanine; (S)-N-α-methylbenzyl-1-propyl-1,4-dihydronicotinamide In acetonitrile for 72h; Ambient temperature; stereospecificity investigated with various amino acids and NAD(P)H model compounds;
With magnesium(II) perchlorate; 6-(1-hydroxymethyl-2-phenylethyl)-1,4,6,7,8,9-hexahydro-1-methyl-pyrido[3,2-c]azepin-5-one In acetonitrile Ambient temperature; other chiral reagents;
With magnesium(II) perchlorate; (4R)-6-(2-methoxyethyl)-2,4-dimethyl-5-(toluene-4-sulfinyl)-1,4-dihydropyridine-3-carboxylic acid methyl ester In acetonitrile for 15h; Heating; other chiral reductants, times;
With magnesium(II) perchlorate; (R,S)-<10>(2,5)pyridinophane-1-methyl-1,4-dihydro-3-(1-hydroxymethylisopropylcarbamoyl) In acetonitrile at 75℃; for 6h; also with (S,S) reagent; other reaction conditions;
With magnesium(II) perchlorate; 1,4-dihydropyridine-cyclophane In acetonitrile at -20℃; influence of temperature and the amount Mg(ClO4)2 upon reduction;
With (+)-α-isopinocampheyl-tert-butylchloroborane In tetrahydrofuran at -25℃; for 1h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With Eapine-Borane at 25℃; for 72h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With magnesium(II) perchlorate; 1-(phenyl-2-ethyl)-7-methyl-3,5-N,N-bis-[(S)-(1-benzylhydroxyethyl)aminocarbonyl]-4,7-dihydropyrrolo[2,3-b]pyridine In acetonitrile for 12h; Ambient temperature;
With potassium 9-O-(1,2:5,6-di-O-isopropylidene-α-D-glucofuranosyl)-9-boratabicyclo<3.3.1>nonane In tetrahydrofuran at -78℃; for 10h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With diisobutylaluminium hydride; (S)-1-methyl-2-<(piperidin-1-yl)-methyl>pyrrolidine; tin(ll) chloride In dichloromethane at -100℃; for 0.333333h; Yield given. Yields of byproduct given;
With magnesium(II) perchlorate; (4S,14S)-4,14-di-(2-propyl)-19-methyl-6,9,12-trioxa-3,15,19-triazabicyclo<15.3.1>heneicosa-17,20-diene-2,5,13,16-tetrone In chloroform; acetonitrile Ambient temperature; dark; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With 2,2'-iminobis[ethanol]; (-)-diisopinocamphenylborane chloride 1) THF, -25 deg C, 1 h; 2) ethyl ether, 2 h; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;
With magnesium(II) perchlorate; (S)-3-(N,N-dimethylcarbamoyl)-1,2,4-trimethyl-1,4-dihydropyridine In [D3]acetonitrile -25 degC to r.t, 1 h;
With 9-O-(1,2-isopropylidene-5-deoxy-α-D-xylofuranosyl)-9-boratabicyclo<3.3.1>nonane potassium In tetrahydrofuran at -78℃; for 50h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With lithium aluminium tetrahydride; ethanol; complex prepd. from (S)-2,2'-dihydroxy-4,5,6,4',5',6'-hexamethoxybiphenyl In tetrahydrofuran 1.) -100 deg C, 2 h, 2.) from -100 to -78 deg C, overnight; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With (+)-diiso-2-ethylapophosphate pinacylboraneheptane In ethyl acetate at -25℃; for 1h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With [Ru{(S)-MeO-BIPHEP}Br2]; hydrogen In methanol at 50℃; for 48h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With perchloric acid; hydrogen In methanol at 30℃; for 70h; Yield given. Yields of byproduct given;
With hydrogen In methanol at 25℃; for 100h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With magnesium(II) perchlorate; 1-benzyl-3-N-(3-deoxy-1,2-O-isopropylidene-α-D-glucofuranos-3-yl)carbamoyl-1,4-dihydropyridine In acetonitrile for 168h; Ambient temperature; Yield given. Yields of byproduct given;
With magnesium chlorite; 1-benzyl-3-N-(3-deoxy-1,2-O-isopropylidene-α-D-glucofuranos-3-yl)carbamoyl-1,4-dihydropyridine In acetonitrile for 168h; Ambient temperature; Yield given. Yields of byproduct given;
With <(-)-2,2'-bis(diphenylphosphino)-4,4',6,6'-tetramethyl-3,3'-bibenzo<b>thiophene>RuCl2; hydrogen In methanol at 25℃; for 100h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With magnesium(II) perchlorate; (S)-5-N(1-hydroxymethyl-2-phenylethyl)carboxamido-1-ethyl-7-methyl-4,7-dihydropyrrolo<2,3-b>pyridine In acetonitrile at -35℃; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With magnesium(II) perchlorate; 1,12-oxo-2,20-diaza-3-methoxycarbonyl-11-oxa-20,23-dihydro<4.9>metaparacyclophane In acetonitrile at 20℃; for 72h; Yield given;
With sodium tetrahydroborate; L-Tartaric acid In tetrahydrofuran at -20℃; for 17h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With magnesium(II) perchlorate; (S)-2-(N-methyl-4,7-dihydrothieno<2,3-b>pyridine-5-carbonyl)aminobutan-1-ol In acetonitrile for 72h; further reagents, further temperatures, solvents and Mg(ClO4)2 concentrations; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With Alpine borane at 25℃; for 72h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With NADH model substance 2b; magnesium(II) In acetonitrile at 60℃; Yield given;
With K 9-O-DIPGF-9-BBNH In tetrahydrofuran at -78℃; for 10h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With K-Glucuride Yield given. Title compound not separated from byproducts;
With 3-pinanyl-9-borabicyclo[3.3.1]nonane at 25℃; for 24h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With 3-pinanyl-9-borabicyclo[3.3.1]nonane at 25℃; for 24h; Yield given. Yields of byproduct given;
With magnesium(II) perchlorate; (R)-3-(N,N-dimethylcarbamoyl)-1,2,4-trimethyl-1,4-dihydropyridine In [D3]acetonitrile -25 degC to r.t, 1 h;
With magnesium(II) perchlorate; 1-methyl-6-<(S)-1-bezylhydroxyethyl>-1,4,5,6,7,8-hexahydro-5-oxo-1,6-naphthyridine In acetonitrile at 60℃; for 48h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With (R,R)-Me-DuphosRuBr2; hydrogen In methanol at 50℃; for 48h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With hydrogen; triethylamine In methanol at 30℃; for 90h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With magnesium(II) perchlorate; 6-(1-hydroxymethyl-2-phenylethyl)-1,4,6,7,8,9-hexahydro-1-methyl-pyrido[3,2-c]azepin-5-one In acetonitrile Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With magnesium(II) perchlorate; (4R)-6-(2-methoxyethyl)-2,4-dimethyl-5-(toluene-4-sulfinyl)-1,4-dihydropyridine-3-carboxylic acid methyl ester In acetonitrile for 15h; Heating; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With magnesium(II) perchlorate; 1-PhCH2-3-N-[(1S,2R)-2-HOCH2C6H10]NHCO-1,4-dihydropyridine In acetonitrile at 20℃; Title compound not separated from byproducts;
With 1,2-bis(t-butylmethylphosphino)ethane; hydrogen In methanol; water at 70℃; for 10h; Yield given; Yields of byproduct given;
With <Ir(COD)2>(+)BF4(-); (1R,2R)-(+)-N,N'-dimethyl-1,2-diphenyl-1,2-ethylenediamine; hydrogen In tetrahydrofuran at 50℃; for 15h; Yield given; Yields of byproduct given. Title compound not separated from byproducts;
With magnesium(II) at -30 - 20℃; Title compound not separated from byproducts;
With tetrafluoroboric acid; RuCl[(-)-N,N'-Me2-3,3'-bis(Ph2P)-2,2'-biindole](C6H6); hydrogen In methanol at 35℃; for 24h;
With magnesium(II) perchlorate; chiral hexahydroazepino[4,3-b]quinoline-based NADH model In acetonitrile at 20℃; for 24h; Title compound not separated from byproducts;
With magnesium(II) perchlorate; (aS,1S,4R)-[4-2H]-quinolino[3,2-c]benz[c]azepin-3-one deriv In acetonitrile Title compound not separated from byproducts;
With magnesium(II) perchlorate; chiral atropisomeric lactam In acetonitrile at 20℃; for 24h; dark; Title compound not separated from byproducts;
With hydrogen In methanol at 50℃; for 21h;
With magnesium(II) perchlorate; NADH model with (S)-phenylalaninol as chiral auxiliary In acetonitrile at 20℃; for 24h; Title compound not separated from byproducts;
With (-)-diisopinocamphenylborane chloride In tetrahydrofuran at -78℃; for 2h; Title compound not separated from byproducts;
With [Ir(1,5-cyclooctadiene)2]PF6; hydrogen; (1R,2R)-(+)-N,N'-dimethyl-1,2-diphenyl-ethylenediamine In tetrahydrofuran at 50℃; for 15h; Title compound not separated from byproducts;
With magnesium(II) perchlorate; (aS,1S,4R)-quinolinium salt In acetonitrile at 20℃; Title compound not separated from byproducts;
With magnesium(II) perchlorate; (aS,1S,4S)-quinolinium salt In acetonitrile at 20℃; Title compound not separated from byproducts;
With formic acid; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; triethylamine In N,N-dimethyl-formamide at 25℃; for 3h;
With magnesium(II) perchlorate; macrocyclic compound with dihydropyridine fragments In dichloromethane at 20℃; for 24h;
With hydrogen In methanol at 50℃; for 24h; Title compound not separated from byproducts;
With iso-cinchonidine; hydrogen In toluene at 25℃; for 1h;
With [Rh(COD)(S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine]-CF3SO3; hydrogen In methanol at 39.85℃; for 2h;
With 5% platinum on alumina; hydrogen; Cinchonidin In toluene at -10.15℃; for 0.5h;
With hydrogen bromide; hydrogen; (R)-(6,6′-dimethoxy-[1,1′-biphenyl]-2,2′-diyl)bis(diphenylphosphine) In methanol at 50℃; for 24h; Title compound not separated from byproducts;
With (S,S)-(-)-2,2'-bis[(R)-(N,N-dimethylamino)(phenyl)methyl]-1,1'-bis[di(3,5-dimethyl-4-methoxyphenyl)phosphine]ferrocene; hydrogen In methanol at 25℃; for 22h; Title compound not separated from byproducts;
With methanesulfonic acid; hydrogen; lithium bromide In methanol at 40℃; Title compound not separated from byproducts;
With magnesium(II) perchlorate; (R)-1-methyl-3-(p-toluenesulfinyl)-1,4-dihydroquinoline In acetonitrile at 20℃; for 24h;
With (1R,2R)-N-p-toluenesulfonyl-1,2-di(4-methoxyphenyl)ethylenediamine; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; triethylamine In dichloromethane at 28℃; for 2.5h; Title compound not separated from byproducts;
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; (S,S)-N-(1-naphthylSO2)-1,2-ethylenediamine dendritic ligand; triethylamine In dichloromethane at 28℃; for 2.5h; Title compound not separated from byproducts;
With potassium phosphate buffer; Rhodotorula sp. AS22241 at 30℃; for 6h; Title compound not separated from byproducts;
With magnesium(II) perchlorate; chiral 1,4-dihydronicotinamide In acetonitrile at -35℃; for 72h;
With hydrogen; 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate In methanol at 20℃; for 20h; Title compound not separated from byproducts;
With copper(II) bis(trifluoromethanesulfonate); diisobutyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; (4S,4S')-(-)-2,2'-(1-methylethylidene)bis[4,5-dihydro-4-(phenylmethyl)oxazole] In chloroform at 20℃; for 12h; Title compound not separated from byproducts;
With magnesium(II) perchlorate; (aS,1S,4R)-quinolinium salt In acetonitrile at 20℃; for 48h; Title compound not separated from byproducts;
With (Rs)-1-methyl-3-(tert-butylsulfinyl)-1,4-dihydropyridine; magnesium(II) perchlorate In acetonitrile at 20℃; for 24h; Title compound not separated from byproducts;
With hydrogen In methanol at 20℃; for 20h;
With magnesium(II) perchlorate In acetonitrile at 20℃; for 72h; Title compound not separated from byproducts.;
With hydrogen In methanol at 50℃; for 24h; Title compound not separated from byproducts.;
With Geotrichum candidum CIOC21062 In phosphate buffer at 30℃; for 24h;
With HCl buffer; isopropyl alcohol; 2-amino-2-hydroxymethyl-1,3-propanediol at 30℃; for 24h; Title compound not separated from byproducts.;
59.2 % ee
With hydrogen In toluene at 25℃; for 20h;
D.11
The experimental procedure is similar to that of Example DI. 2.53 mmol of starting material are always used, and the ratio of substrate to catalyst (sic) is always 200. The reaction parameters and the results are summarized in Table I below.In Examples 5, 11, 16 and 20, toluene (10 ml) is used as solvent. In Examples 6 to 8, 12, 13, 17, 18, 21 and 22, ethanol (10 ml, in Examples 6 and 17 9.5 ml) is used as solvent. In Examples 9, 10, 14, 15 and 19, methanol (10 ml) is used as solvent.
With isopropyl alcohol; NADPH at 30℃; for 24h; Microbiological reaction; aq. buffer; optical yield given as %ee;
Stage #1: methyl 2-oxo-2-phenylacetate With polymethylhydrosiloxane; copper(II) ferrite; (S)-(1,1'-binaphthalene)-2,2'-diylbis(diphenylphosphine) In toluene at 20℃; for 15h;
Stage #2: With tetrabutyl ammonium fluoride; water In tetrahydrofuran; diethyl ether; toluene for 0.5h; optical yield given as %ee; enantioselective reaction;
With Engelhard catalyst; hydrogen; cinchonidine; acetic acid In toluene at 9.84℃; Orito reaction; optical yield given as %ee; enantioselective reaction;
With Engelhard catalyst; hydrogen; cinchonine; acetic acid In toluene at 9.84℃; Orito reaction; optical yield given as %ee; enantioselective reaction;
With magnesium(II) perchlorate; (3R)-3-(4-tert-butyl-benzyl)-1-[bis(trimethylsilyl)methyl]-3-(N-methyl-1,4-dihydronicotinamido)-azetidin-2-one In [D3]acetonitrile at 20℃; for 18h; Inert atmosphere; Darkness; optical yield given as %ee;
With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; sodium formate; dodecyltrimethylammonium bromide; (-)-(1S,2S)-N-(2,4,6-triisopropybenzenesulfonyl)-1,2-diphenylethylenediamine In water at 0℃; for 22h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;
18 % ee
With hydrogen In acetic acid at 20℃; for 1 - 1.16667h;
13
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
78 % ee
With hydrogen In toluene at 20℃; for 1 - 1.16667h;
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
51 % ee
With hydrogen In acetic acid at 20℃; for 1 - 1.16667h;
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
31 % ee
With hydrogen In toluene at 20℃; for 1 - 1.16667h;
B19
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
8 % ee
With hydrogen In toluene at 20℃; for 1 - 1.16667h;
B20
EXAMPLES B13-B24; Hydrogenation of methyl phenylketoacetate [0087]; The procedure of Example B1 is followed using methyl phenylketoacetate. The results are reported in Table 2.
In 2-methyltetrahydrofuran; at 30℃; for 0.0466667h;
Molecular concentration of methyl mandelate and phenylmagnesium bromide dissolved in 2-methyltetrahydrofuranIs a 1 mol / L methyl mandelate solution and a molar concentration of 1 mol / L phenyl magnesium bromide solution;The prepared methyl mandelate solution and the phenylmagnesium bromide solution are respectively input into the first microchannel reactor through a metering pump for main reaction.The reaction solution obtained after the reaction flows directly into the second microchannel reactor.While the reaction solution flows into the second microchannel reactor, the aqueous solution of nitric acid is fed to the second microchannel reactor through a metering pump for quenching reaction.After the quenching reaction is completed, a reaction liquid is obtained, and the reaction liquid flows out to the receiver in a continuous state of a highly dispersed phase, and the reaction liquid in the receiver is separated into an organic phase.The organic phase was dried over anhydrous magnesium sulfate and concentrated under reduced pressure.Recrystallization from toluene to give the finished (S)-(-)-1,1,2-triphenyl-1,2-ethanediol;The main reaction residence time in the first microchannel reactor is 2.8 min.The reaction temperature is 30 C,The molar ratio of the input of the mandelic acid methyl ester solution and the phenylmagnesium bromide solution is 1:1.2;The quenching reaction in the second microchannel reactor has a residence time of 1 min.The quenching reaction temperature is 5 C, and the molar concentration of the aqueous nitric acid solution is 1 mol/L.The molar input of nitric acid is 1.16 times that of phenyl magnesium bromide;The total conversion rate is 100%.The product (S)-(-)-1,1,2-triphenyl-1,2-ethanediol yield was 93%.
With (3R,4S)-4-(3,5-dinitrobenzamido)-1,2,3,4-tetrahydrophenanthren-3-yl covalently linked to 3-propyl silica surface In hexane; acetic acid; isopropyl alcohol at 25℃; Resolution of racemate;
With tetraproline chiral stationary phase packed on HPLC column In hexane; isopropyl alcohol Resolution of racemate;
With cellulose-modified silica gel In hexane; isopropyl alcohol Resolution of racemate;
With cellulose (3,5-dimethylphenyl)carbamate chiral stationary phase 1 In hexane; isopropyl alcohol at 20℃; Resolution of racemate;
The sample solution was prepared by dissolving the racemates in a hexane/IPA (90/10, v/v) mixture. The column was 25 cm long with an internal diameter of 0.46 cm, hexane/IPA or hexane/IPA/THF or hexane/IPA/chloroform were used as the mobile phase, the flow rate was 1.0 or 0.5mL/min at 20 C and the detection wavelength was set to 214 or 254 nm for the test solutes. The mobile phases were filtered and sonicated prior to use. The void time of the columns was determined by 1,3,5-tri-tert-butylbenzene.
With GC column of permethylated mono-6-deoxy-6-(pyridin-1-ium)-α-cyclodextrin trifluoromethanesulfonate at 140℃; Resolution of racemate;
Resolution of racemate;
Multi-step reaction with 2 steps
1: Dess-Martin periodane / dichloromethane / 0 °C
2: cyclohexanone monooxygenase mutant L143F from Acinetobacter sp. NCIMB 9871 in Escherichia coli whole-cell culture medium / acetonitrile / 20 °C / Inert atmosphere; Microbiological reaction; Enzymatic reaction
Multi-step reaction with 2 steps
1: oxygen; dipropylene glycol dimethyl ether / 120 °C
2: C31H36N2O2RuS; sodium formate / methanol; water / 12 h / 50 °C / Inert atmosphere
With chiral stationary phase immobilized tris(3,5-dimethylphenylcarbamate) of cellulose (DMPCC) on silica gel (Nucleosil 4,000 Å, 10 μm) In hexane; isopropyl alcohol Resolution of racemate;
F.1
(S)-2-hydroxy-λ/-methyl-2-phenyl-acetamide Methyl (S)-(+)-mandelate (17.000 g; 102.304 mmol) was dissolved in a 2.0 M solution of methylamine in MeOH (230 ml; 460 mmol) and kept at rt for 1 day. Another portion of methylamine in MeOH (10 ml; 20 mmol) was added. A third portion of methylamine in MeOH (10 ml; 20 mmol) was added one day later. After additional 24h the reaction mixture was concentrated to dryness under reduced pressure to give the desired amide (S)-2- hydroxy-λ/-methyl-2-phenyl-acetamide as pale yellow crystals which were used without further purification.LC-MS: tR = 0.52 min.; [M+H]+ = 166 g/mol.
Stage #1: (S)-Methyl mandelate; methylamine In water at 20 - 30℃;
Stage #2: With hydrogenchloride In water
5
To a solution of methylamine (40 % in water, 3.8 equivalents) is added, at ambient temperature, methyl (S)-mandelate (1.0 equivalent; commercially available), while keeping the temperature below 30 0C and stirred at ambient temperature until full conversion is achieved. After neutralisation with aqueous hydrochloric acid the aqueous solution is saturated with sodium chloride and extracted several times with dichloromethane. The organic layers are combined and the water is removed by azeotropic distillation.
In methanol at 20℃; for 72h;
C.1
C. Synthesis of toluene-4-sulfonic acid (S)-methylcarbamoyl-phenyl-methyl ester:; 1. Synthesis of (S)-2-hydroxy-N-methyl-2-phenyl-acetamide:; Methyl (S)-(+)-mandelate (17 g) is dissolved in a solution of methylamine in methanol (230 mL, 2.0 M) and kept at RT for 1 d. Another portion of methylamine in methanol (10 mL, 2.0 M) is added. A third portion of methylamine in methanol (10 mL, 2.0 M) is added one day later. After additional 24 h the solvents are removed in vacuo to give the desired mandelamide as pale yellow crystals, which are used without further purification. LC-MS: rt = 0.52 min, 166 (M+1, ES+).
In water at 20 - 30℃;
5
Step 5: synthesis of (S)-mandelamid (compound 5); To a solution of methylamine (40% in water, 3.8 equivalents) is added, at ambient temperature, methyl (S)-mandelate (1.0 equivalent; commercially available), while keeping the temperature below 30° C. and stirred at ambient temperature until full conversion is achieved. Excess methylamine is removed by azeotropic distillation. Alternatively, after neutralisation with aqueous hydrochloric acid the aqueous solution is saturated with sodium chloride and extracted several times with dichloromethane. The organic layers are combined and the water is removed by azeotropic distillation.
In methanol at 20℃; for 72h; Inert atmosphere;
16; E.1
Methyl (S)-(+)-mandelate (17.000 g; 102.304 mmol) was dissolved in a 2.0 M solution of methylamine in MeOH (230 ml; 460 mmol) and kept at rt for 1 day. Another portion of methylamine in MeOH (10 ml; 20 mmol) was added. A third portion of methylamine in MeOH (10 ml; 20 mmol) was added one day later. After additional 24 h the reaction mixture was concentrated to dryness under reduced pressure to give the desired amide (S)-2-hydroxy-N-methyl-2-phenyl-acetamide as pale yellow crystals which were used without further purification. LC-MS: tR=0.52 min.; [M+H]+=166 g/mol.
In methanol at 20℃; for 72h;
E.E.1
E. Synthesis of electrophiles Z-CHPh-C(O)NHFM; E.1 Synthesis of toluene-4-sulfonic acid (S)-methylcarbamoyl-phenyl-methyl ester; (S)-2-hydroxy-Λ/-methyl-2-phenyl-acetamide; Methyl (S)-(+)-mandelate (17.000 g; 102.304 mmol) was dissolved in a 2.0 M solution of methylamine in MeOH (230 ml; 460 mmol) and kept at rt for 1 day. Another portion of methylamine in MeOH (10 ml; 20 mmol) was added. A third portion of methylamine inMeOH (10 ml; 20 mmol) was added one day later. After additional 24h the reaction mixture was concentrated to dryness under reduced pressure to give the desired amide (S)-2- hydroxy-Λ/-methyl-2-phenyl-acetamide as pale yellow crystals which were used without further purification. LC-MS: tR = 0.52 min.; [M+H]+ = 166 g/mol.
With oxygen In chloroform at 20℃; for 28h; Resolution of racemate; enantioselective reaction;
46%
With 2,2,6,6-tetramethyl-piperidine-N-oxyl; N,N’-bis(salicylidene)-1,1’-binaphthyl-2,2’-diamine; oxygen; cobalt(II) diacetate tetrahydrate In toluene at 90℃; for 11h; optical yield given as %ee; enantioselective reaction;
With oxygen In acetone for 9h; Resolution of racemate; optical yield given as %ee;
82 % ee
With [(2S,2’S)-1,1’-bis((3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methyl)-2,2’-bipyrrolidineMnII(OTf)2]; dihydrogen peroxide In acetonitrile at -10℃; Resolution of racemate;
With potassium fluoride; tetrabutyl ammonium fluoride In tetrahydrofuran; water at 70℃; for 7h;
General procedure for ester and acetate hydrolysis
General procedure: To a solution of ester or acetate (1 mmol) in THF (5 mL) was added alkali metal fluoride (2 mmol) followed by quaternary ammonium salt (1 M in THF, 2 mL) and the resultant solution was stirred for 7 h. The reaction mixture was diluted with ethyl acetate (30 mL) and washed with water (2 × 20 mL) followed by brine solution (20 mL). The organic layer was dried over MgSO4 and concentrated under reduced pressure to get a crude compound, which was triturated with hexane to get the corresponding product in 60-95 % yield.
With lipase from Candida antarctica (isoform B) immobilized on octyl glyoxyl agarose beads; sodium phosphate at 25℃; Enzymatic reaction;
With octyl-agarose immobilized lipase from Rhizomucor miehei; glycine; calcium chloride at 25℃; Enzymatic reaction;
With lipase from Rhizomucor miehei immobilized on octyl-divinyl sulfone agarose support In aq. phosphate buffer at 25℃; Enzymatic reaction;
2.8.1. Hydrolysis of R or S methyl mandelate
General procedure: 50 mM solutions of R or S methyl mandelate in 50 mM sodium phosphate buffer at pH 7 were prepared. Reactions were started by adding 1 g of the lipase preparations into 5 mL of the substrate solution. The suspensions were maintained at 25 °C under continuous stirring. The reactions were followed by RP-HPLC (Spectra Physic SP 100 coupled with an UV detector Spectra Physic SP 8450) using a Kromasil C18 (15 cm × 0.46 cm) column. Samples (20 L) were injected and eluted at a flow rate of 1.5 mL/min using acetonitrile/10 mM ammonium acetate (35:65, v/v) at pH 2.8 as mobile phase and UV detection was performed at 230 nm. The retention times of the different compounds were: acid: 3 min, ester: 7 min. The enzyme activity was expressed in mol of mandelic acid per minute and mg of enzyme under the conditions described above. Activity was determined by triplicate, using a maximum conversion of 20-30%. The data are given as average values.
Stage #1: benzylamine With Sphingomonas sp. HXN-200 lipase expressed in Escherichia coli cells In hexane; water at 30℃; for 0.0833333h; Enzymatic reaction;
Stage #2: (RS)-methyl mandelate In hexane; water at 30℃; for 1h; Enzymatic reaction; enantioselective reaction;