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Product Details of [ 2584-71-6 ]

CAS No. :2584-71-6 MDL No. :MFCD00005252
Formula : C5H9NO3 Boiling Point : -
Linear Structure Formula :HNCH(COOH)CH2CHOHCH2 InChI Key :PMMYEEVYMWASQN-QWWZWVQMSA-N
M.W : 131.13 Pubchem ID :440014
Synonyms :
H-D-cis-Hyp-OH
Chemical Name :H-D-cis-Hyp-OH

Calculated chemistry of [ 2584-71-6 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.8
Num. rotatable bonds : 1
Num. H-bond acceptors : 4.0
Num. H-bond donors : 3.0
Molar Refractivity : 33.69
TPSA : 69.56 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) : -9.35 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.66
Log Po/w (XLOGP3) : -3.17
Log Po/w (WLOGP) : -1.59
Log Po/w (MLOGP) : -3.44
Log Po/w (SILICOS-IT) : -0.67
Consensus Log Po/w : -1.64

Druglikeness

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

Water Solubility

Log S (ESOL) : 1.41
Solubility : 3370.0 mg/ml ; 25.7 mol/l
Class : Highly soluble
Log S (Ali) : 2.28
Solubility : 24800.0 mg/ml ; 189.0 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : 0.66
Solubility : 597.0 mg/ml ; 4.55 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.23

Safety of [ 2584-71-6 ]

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 [ 2584-71-6 ]

* 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 [ 2584-71-6 ]
  • Downstream synthetic route of [ 2584-71-6 ]

[ 2584-71-6 ] Synthesis Path-Upstream   1~34

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Reference: [1] Patent: WO2018/20358, 2018, A1,
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YieldReaction ConditionsOperation in experiment
57%
Stage #2: With hydrogenchloride In water
Synthetic access to the two additional stereoisomers of the pro4 monomer class has been established. Using a controlled epimerization procedure[34], 30 grams of trans-4-hydroxy-(L)-proline 5 were converted to the diastereomer cis-4-hydroxy-(D)-proline 14 with 57percent isolated yield. By carrying this material through the synthesis described in Scheme 1, synthesis of the other two enantiomers of the pro4 building block class 3:pro4(2R4R) and 4:pro4(2R4S) can be accomplished. (Scheme 3)
44.5%
Stage #1: at 50 - 120℃; for 5.5 h;
Stage #2: at 120℃; for 3 h;
A mixture of AcOH (628.70 g, 10.47 mol) and Ac2O (203.45 g, 1.99 mol) was heated to 50 C, then (2S, 4R)-4-hydroxypyrrolidine-2-carboxylic acid (47.00 g, 358.42 mmol) was added in one portion. The mixture was heated to 120 C and stirred for 5.5 h. After cooling to r.t., the solvent was removed. The residue was dissolved in HCl (650 mL), and then the mixture was heated to 120 C and stirred for 3 h. Then activated charcoal (2.5 g) was added, the hot mixture was filtered immediately through a Celite layer and the cake was washed with hot water. The colorless solution was neutralized with triethylamine and evaporated to dryness. The crude product was refluxed in ethanol (2500 mL) and water was added carefully to the boiling mixture until the solid disappeared (but the solution remained still a little turbid). The solution was thenyleft to stand overnight at -20 C to give white crystals, which were filtered off and washed with cold ethanol afford the title compound (22.00 g, 44.5percent) as a white solid.
570 mmol
Stage #1: With acetic anhydride In acetic acid for 24 h; Reflux
Stage #2: for 24 h; Reflux
 Trans-4-hydroxyproline (100g, 763 mmol) was dissolved in acetic acid (1.0 L) and acetic anhydride (500mL), and refluxed for 24 h. The reaction was then distilled to remove approximately 1 L of solvent, and the remaining solvent removed in vacuo. The compound was redissolved in 2 M HCl (1.0 L) and refluxed for another 24 h, at which time the solvent was removed in vacuo utilizing toluene as an azeotrope. The product was subsequently dissolved in EtOH (1.0 L) and TEA (106 mL), and heated to ~70 °C, after which H2O wasadded until a dark, clear solution was obtained. This solution was left to cool to room temperature, and then placed in a -20 °C freezer overnight. Theresulting crystals were collected via vacuum filtration and washed with cold EtOH to yield 570 mmol of cis-4-hydroxyproline.Recrystallization can be repeated as necessary if there is NMR evidence of trans-4-hydroxyproline.
Reference: [1] Tetrahedron Asymmetry, 2003, vol. 14, # 20, p. 3141 - 3152
[2] Tetrahedron Asymmetry, 2002, vol. 13, # 2, p. 197 - 201
[3] Tetrahedron, 2009, vol. 65, # 4, p. 862 - 876
[4] Patent: US2004/77879, 2004, A1, . Location in patent: Page 13
[5] Patent: WO2018/13867, 2018, A1, . Location in patent: Paragraph 339
[6] Organic Letters, 2000, vol. 2, # 56, p. 4161 - 4164
[7] Journal of Biological Chemistry, 1952, vol. 195, p. 383,384
[8] Chemical and Pharmaceutical Bulletin, 1999, vol. 47, # 11, p. 1650 - 1654
[9] Journal of Organic Chemistry, 2007, vol. 72, # 1, p. 288 - 291
[10] Tetrahedron Asymmetry, 2002, vol. 13, # 2, p. 197 - 201
[11] Tetrahedron Letters, 2010, vol. 51, # 41, p. 5375 - 5377
[12] Tetrahedron Letters, 2016, vol. 57, # 44, p. 4882 - 4884
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YieldReaction ConditionsOperation in experiment
253 mg With water; sodium hydroxide In ethanol for 2 h; A solution of 5a (600 mg, 2.41 mol) in ethanol (9 mL)was subjected to hydrogenation under 50 psi hydrogen pressure in presence of10percent Pd(OH)2 (150 mg) for 3 h. The catalyst was filtered off and thesolution evaporated to dryness. Crude charged with 6 mL, 1M NaOH solution andstirred for 2 h. The reaction mass acidified with acetic acid to pH ~ 5 andpurified with Indion 225 H resin, product eluted in 5percent aqueous ammonia. Productfraction evaporated to get solid, which was further purified with ethanol (5 mL)to afford 253 mg of with 80percent yield.MP = 248-251 °C(decomposition), [α]D25 = +55.87° (c 1.0, H2O),lit.3, [α]D25 = +58.6° (c 0.65, H2O).1H NMR (400 MHz, D2O): δ ppm2.18-2.23 (m, 1H), 2.42-2.49 (m, 1H), 3.32 (dd, J = 3.9 Hz, 1H), 3.41 (d, J = 12.3 Hz, 1H), 4.16 (dd, J = 3.9 Hz, 1H), 4.53 (m, 1H).; 13CNMR (100 MHz, D2O): δ ppm 37.06,82.85, 59.59, 69.05, 174.43.; IR: 3213, 1633, 1564, 1433, 1383.; HRMS (ESI):Calcd for C5H8O3 (M-H)+ 130.0504, Found130.0501. MP = 248-251 °C (decomposition), [α]D25= +55.87° (c 1.0, H2O), lit.3, [α]D25= +58.6° (c 0.65, H2O).
Reference: [1] Tetrahedron Letters, 2015, vol. 56, # 24, p. 3743 - 3746
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Reference: [1] Tetrahedron Asymmetry, 2002, vol. 13, # 2, p. 197 - 201
[2] Journal of Organic Chemistry, 2007, vol. 72, # 1, p. 288 - 291
[3] Journal of Fluorine Chemistry, 2008, vol. 129, # 9, p. 781 - 784
  • 5
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Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
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Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
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Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
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Reference: [1] Helvetica Chimica Acta, 1986, vol. 69, p. 1704 - 1710
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Reference: [1] Advanced Synthesis and Catalysis, 2001, vol. 343, # 6-7, p. 587 - 590
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Reference: [1] Tetrahedron Asymmetry, 1996, vol. 7, # 3, p. 825 - 830
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Reference: [1] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 11, p. 2517 - 2525
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Reference: [1] Tetrahedron Letters, 2015, vol. 56, # 24, p. 3743 - 3746
  • 13
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Reference: [1] Advanced Synthesis and Catalysis, 2001, vol. 343, # 6-7, p. 587 - 590
  • 14
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Reference: [1] Tetrahedron Asymmetry, 1996, vol. 7, # 3, p. 825 - 830
  • 15
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Reference: [1] Tetrahedron Asymmetry, 2002, vol. 13, # 2, p. 197 - 201
  • 16
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Reference: [1] Nucleosides and Nucleotides, 1999, vol. 18, # 3, p. 493 - 508
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Reference: [1] Journal of Biological Chemistry, 1952, vol. 195, p. 383,384
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YieldReaction ConditionsOperation in experiment
190 g With sodium hydrogencarbonate; sodium carbonate In acetone at 22℃; for 15 h; Cooling with ice To a 3 L flask were added (25,4R)-4-hydroxypyrrolidine-2-carboxylic acid (87.0 g,663.46 mmol, 1.0 eq.), water (1500 ml), Na2CO3 (141.0 g, 1330 mmol, 2.0 eq.) andNaHCO3 (55.7 g, 663 mmol, 1.0 eq.). Acetone (250 ml) was added to the solution which was then cooled in an ice-water bath. To the mixture was slowly added Cbz-Cl (141.0 g, 829 mmol, 1.25 eq.). After addition, the reaction mixture was warmed gradually to 22 °C and was stirred for 15 h. The reaction mixture was washed with MTBE (600 ml x 2). To the aqueous phase was slowly added aqueous 1 N HCI until pH—2 was achieved. The resulting mixture was extracted with EtOAc (1 L x 3) and the combined organic layer was dried over MgSO4, filtered and concentrated underreduced pressure to provide 190 g of the title compound as an oil, which was taken to the next step without further purification. LCMS: MS = 287.8 (M+H).
Reference: [1] Patent: WO2018/20358, 2018, A1, . Location in patent: Page/Page column 84; 85
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Reference: [1] Journal of Organic Chemistry, 1990, vol. 55, # l, p. 1684 - 1687
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YieldReaction ConditionsOperation in experiment
91%
Stage #1: With sodium hydroxide In tetrahydrofuran; water at 20℃;
Stage #2: With hydrogenchloride In water
A 5 L, 3-necked flask was charged with (i?,/?)-4-hydroxy-pyrrolidine-2- carboxylic acid (300 g, 2.228 mol), di-tert-butyl dicarbonate (499.3 g, 2.228 mol), 50percent (w/w) NaOH (118 mL, 2.228 mol), THF (2 L) and H2O (1 L). The reaction was stirred at RT overnight. To the reaction mixture was added 3N HCl (762 mL, 2.286 mol). The organic and aqueous layers were separated. Brine (1 L) was added to the aqueous layer, which was extracted with THF (1 L). The organic layers were combined, dried over MgSO4 and concentrated to give a wet cake. The wet cake was azeotroped twice with hexane (2 L each) to give the titled compound as a white to off- white solid (469 g, 91percent yield).
77% With sodium hydroxide In tetrahydrofuran; water at 20℃; for 32 h; Step 1 : Preparation of (2R,4R)-l-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (14b) To a solution of (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid (14a) (10 g, 76 mmol) in THFiH^O (125 mL, 2: 1) was added 2.5 M aqueous sodium hydroxide (42.1 mL, 105 mmol) followed by a solution of di-tert-butyl dicarbonate (22.80 g, 104 mmol) in THF: H2O (125 mL, 2: 1) and stirred at room temperature for 32 h. The mixture was concentrated in vacuum to remove the THF and aqueous layer was added acidified with 10percent aqueous potassium hydrogen sulfate solution (150 mL). The resulting mixture was extracted with ethyl acetate, washed with water, brine, dried, filtered, and evaporated to dryness. The resulting semi-solid was crystallized from hot ethyl acetate to afford (2R,4R)-l-(tert- butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (14b) (13.58 g, 58.7 mmol, 77 percent yield) as a white solid; 1H MR (300 MHz, DMSO-i) δ 12.41 (s, 1H, D20 exchangeable), 4.95 (s, 1H, D20 exchangeable), 4.20 (q, J = 5.1 Hz, 1H), 4.14 - 4.02 (m, 1H), 3.48 (dt, J = 10.8, 5.4 Hz, 1H), 3.09 (ddd, J = 10.6, 6.2, 4.2 Hz, 1H), 2.41 - 2.20 (m, 1H), 1.81 (dt, J = 12.8, 5.0 Hz, 1H), 1.37 (d, J = 15.9 Hz, 9H); 1H NMR (300 MHz, MeOH-i) δ 4.34 (ddd, J = 5.8, 4.0, 1.5 Hz, 1H), 4.30 - 4.22 (m, 1H), 3.61 (dd, J = 11.1, 5.6 Hz, 1H), 3.38 - 3.33 (m, 1H), 2.54 - 2.32 (m, 1H), 2.15 - 1.97 (m, 1H), 1.45 (d, J = 12.0 Hz, 9H); MS (ES+) 254.3 (M+Na); MS (ES-) 230.2 (M-1), 461.5 (2M-1); Optical rotation [D = (+) 52.96 [1.065, MeOH].
67% With sodium hydroxide In tetrahydrofuran; water at 20℃; for 18 h; Step C (1):
Preparation of (2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid.
To a suspension of (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid (purchased from Aldrich)(10.0 g, 76.3 mmol) in 2:1 THF:H2O (125 ml) was added a 2.5 molar aqueous sodium hydroxide solution (42.0 ml).
To this mixture was added a solution of Di-tert-butyldicarbonate (22.6 g, 103.6 mmol) in 2:1 THF: H2O (125 ml).
The resulting reaction mixture was stirred at rt for 18 h.
The mixture was then concentrated in vacuo to remove the THF.
To the remaining aqueous mixture was added a 10percent aqueous potassium hydrogen sulfate solution (150 ml).
The resulting mixture was extracted with ethyl acetate.
The organic phase was washed with H2O, sat. aqueous NaCl, dried (MgSO4), and concentrated in vacuo.
The resulting slightly yellow oil was crystallized from hot ethyl acetate to give 11.8 g (67percent) of (2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid as a white solid: 1H NMR (CD3OD, 300 MHz) δ 1.44 (9H, m), 1.99-2.09 (1H, m), 2.35-2.49 (1H, m), 3.32-3.35 (1H, m), 3.60 (1H, dd, J=6, 12 Hz), 4.25 (1H, dd, J=6, 12 Hz), 4.31-4.36 (1H, m).
Step O (1): (2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid. To a suspension of H-D-Cis-Hyp-OH (purchased from Aldrich, 10.0 g, 76.3 mmol) in 2:1 THF:H2O (125 ml) was added a 2.5 molar aqueous sodium hydroxide solution (42.0 ml). To this mixture was added a solution of Di-tert-butyldicarbonate (22.6 g, 103.6 mmol) in 2:1 THF: H2O (125 ml). The resulting reaction mixture was stirred at rt for 18 h. The mixture was then concentrated in vacuo to remove the THF. To the remaining aqueous mixture was added a 10percent aqueous potassium hydrogen sulfate solution (150 ml). The resulting mixture was extracted with ethyl acetate. The organic phase was washed with H2O, sat. aqu. NaCl, dried (MgSO4), and concentrated in vacuo. The resulting slightly yellow oil was crystallized from hot ethyl acetate to give 11.8 g (67percent) of (2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid as a white solid: 1H NMR (CD3OD, 300 MHz) δ 1.44 (9H, m), 1.99-2.09 (1H, m), 2.35-2.49 (1H, m), 3.32-3.35 (1H, m), 3.60 (1H, dd, J=6, 12 Hz), 4.25 (1H, dd, J=6, 12 Hz), 4.31-4.36 (1H, m)
67%
Stage #1: With sodium hydroxide In tetrahydrofuran; water at 20℃; for 18 h;
Step A (1): (2R,4R)-l-(tert-butoxycarbonyl)-4-hydroxvpyrrolidine-2- carboxylic acid.; To a suspension of H-D-Cis-Hyp-OH (purchased from Aldrich, 10.0 g, 76.3 mmol) in 2:1 THF:H2O (125 ml) was added a 2.5 molar aqueous sodium hydroxide solution (42.0 ml). To this mixture was added a solution of Di-tert-butyldicarbonate (22.6 g, 103.6 mmol) in 2:1 THF: H2O (125 ml). The resulting reaction mixture was stirred at rt for 18 h. The mixture was then concentrated in vacuo to remove the THF. To the remaining aqueous mixture was added a 10percent aqueous potassium hydrogen sulfate solution (150 ml). The resulting mixture was extracted with ethyl acetate. The organic phase was washed with H2O, sat. aqu. NaCl, dried (MgSO4), and concentrated in vacuo. The resulting slightly yellow oil was crystallized from hot ethyl acetate to give 11.8 g (67percent) of (2R,4R)-l-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2- carboxylic acid as a white solid: 1H NMR (CD3OD, 300 MHz) δ 1.44 (9H, m), 1.99 - 2.09 (IH, m), 2.35 - 2.49 (IH, m), 3.32 - 3.35 (IH, m), 3.60 (IH, dd, J= 6, 12 Hz), 4.25 (IH, dd, J= 6, 12 Hz), 4.31 - 4.36 (IH, m).; Step C (1): Preparation of (2R,4R)-l-(tert-butoxycarbonyl)-4- hydroxypyrrolidine-2-carboxylic acid.; To a suspension of H-D-Cis-Hyp-OH (purchased from Aldrich)(10.0 g, 76.3 mmol) in 2:1 THFiH2O (125 ml) was added a 2.5 molar aqueous sodium hydroxide solution (42.0 ml). To this mixture was added a solution of Di-tert-butyldicarbonate (22.6 g, 103.6 mmol) in 2:1 THF: H2O (125 ml). The resulting reaction mixture was stirred at rt for 18 h. The mixture was then concentrated in vacuo to remove the THF. To the remaining aqueous mixture was added a 10percent aqueous potassium hydrogen sulfate solution (150 ml). The resulting mixture was extracted with ethyl acetate. The organic phase was washed with H2O, sat. aqu. NaCl, dried (MgSO4), and concentrated in vacuo. The resulting slightly yellow oil was crystallized from hot ethyl acetate to give 11.8 g (67percent) of (2R,4R)-l-(tert-butoxycarbonyl)-4- hydroxypyrrolidine-2-carboxylic acid as a white solid: 1H NMR (CD3OD, 300 MHz) 6 1.44 (9H, m), 1.99 - 2.09 (IH, m), 2.35 - 2.49 (IH, m), 3.32 - 3.35 (IH, m), 3.60 (IH, dd, J= 6, 12 Hz), 4.25 (IH, dd, J= 6, 12 Hz)5 4.31 - 4.36 (IH, m).
61% With sodium hydroxide In tetrahydrofuran-water Step 1:
(2R,4R)-4-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (1)
Cis-4-hydroxy-D-proline (15 g, 114 mmol) was dissolved In 150 mL of THF/H2O (2:1), added 2M aqueous NaOH solution (86 mL, 172 mmol), followed by Boc2O (27 g, 126 mmol).
Reaction was stirred at ambient temperature overnight.
The solution was acidified with 10percent citric acid then extracted with EtOAc (2*250 mL), washed with water, brine, dried organics with MgSO4, filtered and concentrated to give 1 (16 g, 61percent) APCI (AP-): 230.1 (M-H)-.
9.3 g With triethylamine In methanol for 2 h; Reflux A)
(2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid
A mixture of (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid (5.3 g), di-tert-butyl dicarbonate (19 mL), triethylamine (10 mL) and methanol (90 mL) was heated with reflux for 2 hr.
The mixture was allowed to be cooled to room temperature, and the solvent was evaporated under reduced pressure.
The residue was adjusted to pH2 with sodium dihydrogenphosphate (400 mg) and dilute hydrochloric acid under ice-cooling.
The mixture was stirred under ice-cooling for 30 min, and extracted with ethyl acetate/2-propanol (5:1).
The organic layer was sparated, washed with saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound (9.3 g).
1H NMR (300 MHz, DMSO-d6) δ 1.31-1.41 (9H, m), 1.75-1.86 (1H, m), 2.23-2.39 (1H, m), 3.03-3.15 (1H, m), 3.43-3.54 (1H, m), 4.03-4.13 (1H, m), 4.15-4.25 (1H, m).

Reference: [1] Patent: WO2006/38119, 2006, A1, . Location in patent: Page/Page column 19
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 6, p. 1771 - 1782
[3] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 9, p. 2755 - 2760
[4] Journal of Medicinal Chemistry, 1991, vol. 34, # 9, p. 2787 - 2797
[5] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 6, p. 2501 - 2511
[6] Patent: WO2017/59178, 2017, A1, . Location in patent: Page/Page column 77-78
[7] Patent: US2006/46984, 2006, A1, . Location in patent: Page/Page column 17; 28-29
[8] Patent: WO2006/99352, 2006, A1, . Location in patent: Page/Page column 25; 30
[9] Patent: US2003/162787, 2003, A1,
[10] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 14, p. 2095 - 2100
[11] Chemical Communications, 2004, # 10, p. 1208 - 1209
[12] Patent: US2003/162787, 2003, A1,
[13] Patent: US2003/162787, 2003, A1,
[14] Patent: US2003/162787, 2003, A1,
[15] Patent: US2003/162787, 2003, A1,
[16] Patent: US2003/162787, 2003, A1,
[17] Patent: US2003/162787, 2003, A1,
[18] Patent: US2003/162787, 2003, A1,
[19] Patent: US2003/69297, 2003, A1,
[20] Journal of Fluorine Chemistry, 2008, vol. 129, # 9, p. 781 - 784
[21] Australian Journal of Chemistry, 2015, vol. 68, # 9, p. 1365 - 1372
[22] Patent: EP2933247, 2015, A1, . Location in patent: Paragraph 0365
  • 21
  • [ 1070-19-5 ]
  • [ 2584-71-6 ]
  • [ 135042-12-5 ]
Reference: [1] Journal of Organic Chemistry, 1992, vol. 57, # 14, p. 3783 - 3789
  • 22
  • [ 34619-03-9 ]
  • [ 2584-71-6 ]
  • [ 135042-12-5 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 24, p. 5351 - 5355
  • 23
  • [ 58632-95-4 ]
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  • [ 135042-12-5 ]
Reference: [1] Organic Letters, 2001, vol. 3, # 16, p. 2481 - 2484
  • 24
  • [ 67-56-1 ]
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  • [ 114676-59-4 ]
YieldReaction ConditionsOperation in experiment
100% 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
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YieldReaction ConditionsOperation 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,
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Reference: [1] Synthesis, 1988, # 1, p. 40 - 44
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Reference: [1] Journal of Medicinal Chemistry, 1988, vol. 31, # 8, p. 1598 - 1611
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  • [ 114676-61-8 ]
Reference: [1] Journal of Medicinal Chemistry, 1988, vol. 31, # 8, p. 1598 - 1611
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  • [ 155075-23-3 ]
YieldReaction ConditionsOperation in experiment
100% With sodium hydrogencarbonate In water; toluene at 23℃; for 24.25 h; To a stirred solution of 4R-hydroxypyrrolidine-2R-carboxylic acid (5.02 g, 38.3 mmol, 1 eq. ) and [NAHC03] (8.05 g, 95.8 mmol, 2.5 eq. ) in H20 (85 mL) at 23 [°C] was added a solution of Cbz-Cl (6.28 mL, 44.0 mmol, 1.15 eq. ) in toluene (20 mL) over 15 min period. After 24 h the layers were separated and the aqueous layer was extracted with Et2O (2 x 100 mL) and discarded the combined organic layer. The aqueous layer was then acidified to pH 2 with concentrated [HCI,] and the product was extracted with EtOAc (2 x 100 mL). The organic layer was dried and concentrated in vacuo to give [4R-HYDROXYPYRROLIDINE-1,] [2R-DICARBOXYLIC] acid [1-] benzyl ester 2-methyl ester (9.97 g, [100percent)
Reference: [1] Patent: WO2004/7444, 2004, A2, . Location in patent: Page 139
[2] Collection of Czechoslovak Chemical Communications, 1996, vol. 61, p. S234 - S237
[3] Journal of the American Chemical Society, 1996, vol. 118, # 29, p. 6826 - 6840
[4] Patent: WO2016/11930, 2016, A1,
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  • [ 7732-18-5 ]
  • [ 584-08-7 ]
  • [ 501-53-1 ]
  • [ 2584-71-6 ]
  • [ 155075-23-3 ]
Reference: [1] Patent: US5436229, 1995, A,
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  • [ 7732-18-5 ]
  • [ 584-08-7 ]
  • [ 501-53-1 ]
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  • [ 155075-23-3 ]
Reference: [1] Patent: US5578574, 1996, A,
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Reference: [1] Journal of Medicinal Chemistry, 1999, vol. 42, # 26, p. 5426 - 5436
[2] Patent: WO2011/130383, 2011, A1,
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  • [ 364077-84-9 ]
Reference: [1] Patent: WO2017/59178, 2017, A1,
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  • [ 681128-50-7 ]
Reference: [1] Patent: WO2011/130383, 2011, A1,
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