* 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.
With thionyl chloride In methanol at 0 - 23℃; for 16.025 h;
To a stirred solution [OF 4R-HYDROXYPYRROLIDINE-2R-CARBOXYLIC] acid (10.0 g, 76.3 mmol, [1] eq. ) in [MEOH] (300 mL) at [0 °C] was added SOC12 (10.0 mL, excess) over the course of 1.5 min. The reaction was allowed to warm to [23 °C.] After 16 h the reaction mixture was concentrated in vacuo to give 4R-hydroxypyrrolidine-2R-carboxylic acid methyl ester hydrochloride salt as a white solid (15.9 g, 100percent yield)
90%
at 0 - 20℃; for 72 h;
To a solution of (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid 31.1 (1.0 eq) in MeOH (31 eq) at 0 °C was added S0C12 (1.2 eq) dropwise. The reaction solution was stirred at rt for 72 h. The resulting mixture was concentrated in vacuo to afford the compound 31.2 (90percent yield) as a white solid. LCMS (m/z): 146.0 [M+H] +. 1H NMR (400 MHz, DMSO-i/6) 3: 4.44 (d, J = 6.8 Hz, 1H), 4.33 (s, 1H), 3.70 (s, 3H), 3.03-3.00 (m, 1H), 2.30-2.23 (m, 1H), 2.14-2.09 (m, 1H), 1.17 (t, J = 7.2 Hz, 1H).
Reference:
[1] Patent: WO2004/7444, 2004, A2, . Location in patent: Page 135
[2] Journal of the American Chemical Society, 1996, vol. 118, # 29, p. 6826 - 6840
[3] Patent: WO2011/29046, 2011, A1, . Location in patent: Page/Page column 153; 154
[4] Journal of Medicinal Chemistry, 1988, vol. 31, # 8, p. 1598 - 1611
[5] Journal of Medicinal Chemistry, 1999, vol. 42, # 26, p. 5426 - 5436
[6] Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 5, p. 1399 - 1415
[7] Journal of Organic Chemistry, 2000, vol. 65, # 5, p. 1590 - 1596
[8] Organic letters, 1999, vol. 1, # 10, p. 1513 - 1516
[9] Chemistry - A European Journal, 2010, vol. 16, # 35, p. 10691 - 10706
[10] Organic Letters, 2011, vol. 13, # 16, p. 4442 - 4445
[11] Patent: WO2011/130383, 2011, A1, . Location in patent: Page/Page column 104
[12] Chemistry - A European Journal, 2014, vol. 20, # 13, p. 3813 - 3824
[13] Chemical and Pharmaceutical Bulletin, 2016, vol. 64, # 8, p. 1242 - 1247
2
[ 2584-71-6 ]
[ 114676-59-4 ]
Yield
Reaction Conditions
Operation in experiment
100%
With thionyl chloride In methanol at 10 - 65℃; for 2 h;
To a suspension of (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid (100 g, 0.763 mol) in MeOH (1 L) was added SOd2 (115 g, 0.966 mcI) slowly at 10 °C. Then the reaction was heated at 65 °C for 2 hrs. The mixture was concentrated under high vacuum. The residue was washed with ether, filtered to give the title compound 0350 (138 g, 100percent yield) as a yellow solid.LCMS: 146 [M+H]. tR =0.366 mins. (LCMS condition 3)
113%
With thionyl chloride In methanol
Step A-1. Preparation of an ester compound To a suspension of cis-4-hydroxy-D-proline (16.46 g: 125.5 mmole) in methanol (66 ml), thionylchloride (9.16 ml: 125.5 mmole) is added in a nitrogen atmosphere under ice cooling, and the mixture is stirred at room temperature for 30 minutes. The mixture is further stirred to react at 40° C. for 4 hours to give (2R,4R)-4-hydroxy-2-methoxycarbonylpyrrolidine hydrochloride as crude crystals (25.74 g). Yield: 113percent. Colorless crystals. NMR δ(D2 O) ppm: 2.3 to 2.6(m, 2H), 3.33(s, 1H), 3.4 to 3.5(m, 2H), 3.84(s, 3H), 4.6 to 4.7(m, 2H). IR ν (KBr) cm-1: 3320, 2980, 1728.
Reference:
[1] Patent: WO2015/113452, 2015, A1, . Location in patent: Page/Page column 186; 187
[2] Patent: US5317016, 1994, A,
3
[ 67-56-1 ]
[ 77449-94-6 ]
[ 114676-59-4 ]
Yield
Reaction Conditions
Operation in experiment
100%
at 0 - 75℃; for 4.5 h;
Cis-4-hydroxy-D-proline hydrochloride 3A (12.8 g, 76.38 mmol) was dissolved in anhydrous methanol (120 mL) at room temperature,Cooled to 0 , dichloro sulfoxide (10.27g, 86.31mmol),Heated to 75 ° C, refluxed for 4.5 hours, and allowed to react overnight at room temperature.The solvent was taken off in vacuo to give a white solid 3B (13.83 g, yield 100percent).
Reference:
[1] Patent: TW2017/8221, 2017, A, . Location in patent: Page/Page column 41
[2] Journal of Organic Chemistry, 2009, vol. 74, # 2, p. 513 - 519
[3] Patent: US2009/163472, 2009, A1, . Location in patent: Page/Page column 21
[4] Patent: WO2014/32, 2014, A1, . Location in patent: Page/Page column 64
[5] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 10, p. 2434 - 2437
Reference:
[1] Journal of Medicinal Chemistry, 1988, vol. 31, # 8, p. 1598 - 1611
9
[ 114676-59-4 ]
[ 114676-61-8 ]
Reference:
[1] Journal of Medicinal Chemistry, 1988, vol. 31, # 8, p. 1598 - 1611
10
[ 501-53-1 ]
[ 114676-59-4 ]
[ 155075-23-3 ]
Yield
Reaction Conditions
Operation in experiment
7.4 g
With sodium carbonate In tetrahydrofuran; water at 0 - 20℃; for 2 h;
To a solution of D (17.94 g, 98.8 mmol) and Na2C03 (10.5 g, 98.8 mmol) in THF/H20 (150 mL/50 mL) was added CbzCI (20.2 g, 1 18.56 mmol) at 0 °C and the mixture was stirred at room temperature for 2 h. The mixture was filtered through filter paper and the filtrate was concentrated. Water (200 mL) was added and the product was extracted with EtOAc (100 ml x 3). The combined organic layers were washed with brine, dried (MgS0 ), filtered, and concentrated. The residue was purified by column chromatography (silica gel, PetEther/EtOAc=5/1 -2/1) to get the desired product (7.4 g, 27percent) as a light yellow oil. LC-MS : 279.9 ([M+1]+ ).
Reference:
[1] Journal of the American Chemical Society, 1996, vol. 118, # 29, p. 6826 - 6840
[2] Patent: WO2014/32, 2014, A1, . Location in patent: Page/Page column 64; 65
11
[ 75315-63-8 ]
[ 114676-59-4 ]
[ 155075-23-3 ]
Reference:
[1] Chemistry - A European Journal, 2010, vol. 16, # 35, p. 10691 - 10706
12
[ 114676-59-4 ]
[ 254881-77-1 ]
Reference:
[1] Journal of Medicinal Chemistry, 2000, vol. 43, # 26, p. 4948 - 4963
13
[ 114676-59-4 ]
[ 256487-77-1 ]
Reference:
[1] Journal of Medicinal Chemistry, 1999, vol. 42, # 26, p. 5426 - 5436
[2] Patent: WO2011/130383, 2011, A1,
[3] Patent: TW2017/8221, 2017, A,
5-{(2R,3S,4R)-2-[(1S,2R)-1-Ethoxycarbonyl-2-((2R,3S,4R,5S,6S)-3,4,5-trihydroxy-6-methyl-tetrahydro-pyran-2-yloxy)-propylcarbamoyl]-3,4-dihydroxy-pyrrolidin-1-yl}-5-oxo-pentanoic acid[ No CAS ]
(2S,3R)-2-[((2R,3S,4R)-3,4-Dihydroxy-pyrrolidine-2-carbonyl)-amino]-3-((2R,3S,4R,5R,6S)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran-2-yloxy)-butyric acid ethyl ester[ No CAS ]