32968-78-8|(2S,4R)-4-Hydroxypyrrolidine-2-carboxylic acid hydrochloride| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 32968-78-8 ] Purity: 97% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 32968-78-8 ]

CAS No. :	32968-78-8
Formula :	C₅H₁₀ClNO₃
M.W :	167.59
SMILES Code :	O=C([C@H]1NC[C@H](O)C1)O.[H]Cl
MDL No. :	MFCD09908038
InChI Key :	YEJFFQAGTXBSTI-HJXLNUONSA-N
Pubchem ID :	11205991

Safety of [ 32968-78-8 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 32968-78-8 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
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	40.65
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	69.56 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	-2.37
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.79
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	-3.07
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-0.67
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-1.38

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	0.68
Solubility	802.0 mg/ml ; 4.79 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Highly soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	1.45
Solubility	4700.0 mg/ml ; 28.0 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Highly soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.66
Solubility	763.0 mg/ml ; 4.55 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-9.01 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	2.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.31

Application In Synthesis of [ 32968-78-8 ]

* 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.

Downstream synthetic route of [ 32968-78-8 ]

[ 32968-78-8 ] Synthesis Path-Downstream 1~35

1
[ 14002-51-8 ]
[ 32968-78-8 ]
[ 643001-83-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran; water; at 0 - 20℃; for 18h;	To a solution of commercial L-beta-homohydroxyproline hydrochloride (245 mg, 1.35 mmol), triethylamine (1.13 ml, 8.09 mmol) in water (0.8 ml) and tetrahydrofuran (2 ml) at [0C] under argon, was added dropwise a solution of 4-phenylbenzoyl chloride (438 mg, 2.02 mmol) in tetrahydrofuran [(1] ml). The reaction mixture was allowed to warm to room temperature and was stirred 18 hours. It was then diluted with acetone-ethyl acetate (1-2) and washed with [HC1] [1N.] The organic phase was dried [(MGS04)] and concentrated to afford a mixture of desired product and 4-phenylbenzoyl acid. A small quantity of acid could be obtained by precipitation with ethyl acetate. ['H] NMR (DMSO): 1.82 (m, 1H), 2.11 (m, [1H),] 2.5 (m, [1H),] 2.81 (dd, J=15.6 Hz, [J=3.] 2, [1H),] 3.3 (m, [1H),] 3.51 (dd, [J=11.] 7 Hz, J=2.6 Hz, [1H),] 4.16 (m, [1H),] 4.40 (m, [1H),] 7. [30-8.] 00 (m, 9H). LC/MS: (ESI-): 280 (M-1-C02), 324 [(M-1)] (ESI+): 326 [(M+1)] HPLC purity: 84 %

References: [1]Patent: WO2004/5249,2004,A1 .Location in patent: Page 52-53.

2
[ 24424-99-5 ]
[ 32968-78-8 ]
[ 74844-91-0 ]

Yield	Reaction Conditions	Operation in experiment
4.2 g (57%)	With sodium hydroxide; In tetrahydrofuran; water; ethyl acetate;	i 1-(tert-Butyl) 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate In a flask was dissolved <strong>[32968-78-8](2S,4R)-4-Hydroxy-proline hydrochloride</strong> (5.4 g, 30 mmole) in a mixture of THF (200 ml), water (170 ml) and NaOH (30 ml, 2 M in water, 60 mmole). To this emulsion was added di-tert-butyldicarbonate (Boc2O, 6.54 g, 30 mmole), and the mixture was stirred vigorously for 1 hour. Ether (100 ml) was added and the phases were allowed to separate. The aqueous phase was extracted with an additional 100 ml of ether. The aqueous phase was discarded and the combined organic phases were washed with IM HCl (aq.) and potassium carbonate (saturated, aq.) and brine. The extract was dried with Na2SO4 and was concentrated in vaccuo to give a residue, which was purified on silica (Heptane:EtOAc 5:1 to 3:1 to 1:1 stepwise gradient, spots visualized with I2/MeOH). Evaporation of pure fractions were concentrated in vaccuo to give 4.2 g (57%) of the subtitle compound as a colorless oil. 1H-NMR (400 MHz, CDCl3) delta: 4.50 (1H, bs); 4.45-4.35 (1H, m); 3.74 (3H, s); 3.64 (1H, dd, J 11.7, 4.3 Hz); 3.59-3.42 (1H, m); 2.35-2.20 (1H, m); 2.14-2.03 (1H, m); 1.97 (1H, dd, J 23.3, 3.7 Hz); 1.44 (9H, d, J 18.9 Hz)

References: [1]Patent: US2003/144267,2003,A1 .

3
[ 31162-13-7 ]
[ 32968-78-8 ]
[ 166451-20-3 ]

References: [1]Tetrahedron Letters,2008,vol. 49,p. 1465 - 1468.

4
[ 117573-59-8 ]
[ 32968-78-8 ]
[ 923975-46-6 ]

References: [1]Tetrahedron Letters,2008,vol. 49,p. 1465 - 1468.

5
[ 32968-78-8 ]
[ 166117-56-2 ]
[ 923975-47-7 ]

References: [1]Tetrahedron Letters,2008,vol. 49,p. 1465 - 1468.

6
[ 32968-78-8 ]
[ 790684-90-1 ]
[ 1016556-99-2 ]

References: [1]Tetrahedron Letters,2008,vol. 49,p. 1465 - 1468.

7
[ 32968-78-8 ]
[ 51-35-4 ]

References: [1]Synthesis,2009,p. 143 - 147.

8
[ 67-56-1 ]
[ 32968-78-8 ]
[ 40216-83-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With thionyl chloride; at 0 - 20℃;Reflux;	Example 1 : methyl ("2S,4R)-4-hvdroxy-2-pyrrolidinecarboxylate hydrochloride To a solution of (2S,4R)- 4-hydroxy-2-pyrrolidinecarboxylic acid hydrochloride (1.0 g, 7.6 mmol) in methanol (25 mL) at 0 C was added thionyl chloride (0.83 mL, 1 1.4 mmol). The reaction was warmed to room temperature and heated at reflux overnight. After cooling to room temperature, the reaction mixture was concentrated to dryness to give the title compound (1.2 g, 92%) as a white solid. lH NMR (300 MHz, DMSO-<) delta 9.99 (br. s, 2H), 5.58 (br. s, 1H), 4.49-4.41 (m, 2H), 3.75 (s, 3H), 3.38 (dd, 1H), 3.07 (d, 1H), 2.23-2.04 (m, 2H)
92%	With thionyl chloride; at 0℃;Reflux;	To a solution of <strong>[32968-78-8](2S,4R)-4-hydroxy-2-pyrrolidinecarboxylic acid hydrochloride</strong> (1.0 g, 7.6 mmol) in methanol (25 mL) at 0 C. was added thionyl chloride (0.83 mL, 11.4 mmol). The reaction was warmed to room temperature and heated at reflux overnight. After cooling to room temperature, the reaction mixture was concentrated to dryness to give the title compound (1.2 g, 92%) as a white solid. 1H NMR (300 MHz, DMSO-d6) delta 9.99 (br. s, 2H), 5.58 (br. s, 1H), 4.49-4.41 (m, 2H), 3.75 (s, 3H), 3.38 (dd, 1H), 3.07 (d, 1H), 2.23-2.04 (m, 2H).

References: [1]Organic Letters,2018,vol. 20,p. 162 - 165.
[2]Patent: WO2013/174937,2013,A1 .Location in patent: Page/Page column 74.
[3]Patent: US2015/152048,2015,A1 .Location in patent: Paragraph 0447-0448.

9
[ 138512-74-0 ]
[ 32968-78-8 ]

References: [1]Patent: WO2014/25805,2014,A1 .

10
[ 364750-80-1 ]
[ 32968-78-8 ]

Yield	Reaction Conditions	Operation in experiment
31 g	With hydrogenchloride; In diethyl ether;	Step (i)[3]: To a stirred solution of NBoc diol (57 g, 262.52 mmol) in ether (150 mL) was addedHCl in ether (50 mL) and stirred for overnight. The white solid was filtered and washed withether (50 mL). The filtrate was kept at -0 oc for 6 hand the solid was filtered and washed withether (25 mL). Both batches were combined and dried in the presence of P20s under reducedpressure to constant weight 4 (31 g). 1H NMR (D20): 1.94-2.01 (m, 1H), 2.14-2.19 (m, 1H),3.30-3.48 (m, 2H), 3.71-3.76 (m, 1H), 3.93-4.08 (m, 2H), 4.67-4.75 (m, 1H).

References: [1]Patent: WO2014/25805,2014,A1 .Location in patent: Page/Page column 34.

11
[ 40615-36-9 ]
[ 32968-78-8 ]
C₂₆H₂₇NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%		Synthesis of compound 5; Step(ii)[1]: The reaction was performed in a 5 necked 15 L glass reactor fitted with an overheadstirrer over an ice bath. To a stirred solution of 4 (450 g, 2.94 mole) in acetonitrile (8 L) wereadded Et3N (1 L, 7.2 mole) and ethyl trifluoroacetate (1000 g, 7.04 mole), and stirred at room temperature overnight. The white solid (Et3N.HC1) was filtered over sintered funnel and washedwith ethyl acetate ( 4 L). The organic solution was concentrated followed by co-evaporationwith toluene (2 L x 2) and dried under reduced pressure overnight in a 22 L rotary evaporator toobtain crude product as a gummy mass ( -600 g). Step (ii)[2]: Above obtained crude compound (2.94 mole) was dissolved in 2 L of anhyd.pyridine and transferred to the four necked 15 L flask. Another 6 L of anhyd. pyridine wasadded. This solution was cooled to -5 oc using ice bath followed by addition of DMTr-Cl (1000g, 2.95) portion wise under nitrogen atmosphere over 20 min. and the reaction mixture wasstirred at room temperature overnight. 12 L of water was added while stirring and let it stand for6 h. The compound was settled at the bottom of the flask as a brownish gummy mass. Waterpyridinelayer was decanted using transfer pump and the aqueous layer was extracted with ethylacetate (2 x 5 L). Combined the ethyl acetate extract with the viscous material remained in thereactor, after decanting water layer. Concentration of the solvent gave the correspondingproduct as viscous oil which was used for the next step without purification. Step (ii)[3]: To a stirred solution of trifluoroacetyl compound (2.94 mole) in MeOH (5 L) wasadded KOH (330 g, 5.88 mole) dissolved in water (2 L) drop wise over 30 min. and stirred atroom temperature for 1 h. Concentrated to 3 L volume followed by addition of 15 L of waterand allowed to stand overnight. The product was settled at the bottom as reddish brown viscousoil. Decanted the water using transfer pump followed by addition of 6 L of DCM to dissolve,washed with 5 L of water and separated the organic solvent. Concentration of the solventfollowed by silica gel column chromatography ( 4 Kg silica, eluent: hexane/ethyl acetate andethyl acetate/MeOH) purification gave compound 5 (1000 g, 81 %) as foamy yellowish whitesolid. 1H NMR (CDCb): 1.35-1.42 (m, lH), 1.65-1.70 (m, lH), 2.33 (br s, lH), 2.59-2.62 (m,lH), 2.72-2.75 (m, lH), 2.82-2.91 (m, 2H), 3.36-3.41 (m,lH), 3.71 (s, 6H), 4.1 (br s, lH), 4.525(d, J = 4.0 Hz, lH).

References: [1]Patent: WO2014/25805,2014,A1 .Location in patent: Page/Page column 34; 35.

12
[ 1551527-41-3 ]
[ 32968-78-8 ]
C₃₉H₇₆N₈O₁₀*3ClH [ No CAS ]

References: [1]Patent: WO2014/25805,2014,A1 .

13
[ 1551527-41-3 ]
[ 32968-78-8 ]
[ 1551527-43-5 ]

Yield	Reaction Conditions	Operation in experiment
31 g		Step (iii)[l]: To a stirred solution of acid 8 (28 g, 27.514 mmol) trans hydroxyl prolinol4 (6.3 g,41.27 mmol) and HOBt (16.84 g, 110.06 mmol) in DCM/DMF (250 mL/250 mL) was addedDIEA (17 .75 g, 137.57 mmol) drop wise at room temperature over 5 min. and stirred for 30 min.To the above solution was added HBTU (13.05, 34.39 mmol) portion wise over 10 min. andstirred for 3 h. 100 mL of water was added followed by evaporation of DCM and then 500 mLof water was added and left at standing for 1 h. Decanted the turbid solution and the sticky solidwas ringed with water (100 mL x 3). The gummy material was dissolved 20% MeOH in DCM(500 mL) and concentrated followed by co-evaporation with toluene (100 ml x 2) to obtain thecorresponding product (31 g) as yellowish foamy solid. LCMS: Calculated: 1116.73 (M+),Found: 1117.7 (M++l), 1139.6 (M++Na).

References: [1]Patent: WO2014/25805,2014,A1 .Location in patent: Page/Page column 38.

14
[ 40216-83-9 ]
[ 32968-78-8 ]

References: [1]Patent: WO2014/25805,2014,A1 .

15
[ 32968-78-8 ]
2-methyl-2-propanyl 4-[({(2S,4S)-1-[1-(N,N'-bis[(2-methyl-2-propanyl)oxy]carbonyl}carbamimidoyl)-4-piperidinyl]carbonyl}-4-[4-(methylsulfonyl)-1-piperazinyl]-2-pyrrolidinyl}carbonyl)amino]benzoate [ No CAS ]