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Chemical Structure| 22929-52-8 Chemical Structure| 22929-52-8

Structure of Dihydrofuran-3(2H)-one
CAS No.: 22929-52-8

Chemical Structure| 22929-52-8

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Synonyms: 3-Oxotetrahydrofuran

4.5 *For Research Use Only !

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Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

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Product Details of [ 22929-52-8 ]

CAS No. :22929-52-8
Formula : C4H6O2
M.W : 86.09
SMILES Code : O=C1CCOC1
Synonyms :
3-Oxotetrahydrofuran
MDL No. :MFCD07778393
InChI Key :JLPJFSCQKHRSQR-UHFFFAOYSA-N
Pubchem ID :529392

Safety of [ 22929-52-8 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319
Precautionary Statements:P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235
Class:3
UN#:1224
Packing Group:

Computational Chemistry of [ 22929-52-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 20.51
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

26.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.15
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

-0.37
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

-0.02
Log Po/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.

-0.72
Log Po/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

1.43
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.29

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-0.14
Solubility 62.3 mg/ml ; 0.723 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

0.28
Solubility 164.0 mg/ml ; 1.91 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

-0.51
Solubility 26.5 mg/ml ; 0.308 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.

-7.09 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)

1.13

Application In Synthesis of [ 22929-52-8 ]

* 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 [ 22929-52-8 ]

[ 22929-52-8 ] Synthesis Path-Downstream   1~54

  • 1
  • [ 22929-52-8 ]
  • [ 4301-15-9 ]
  • bis-(3-hydroxy-tetrahydro-[3]furyl)-acetylene [ No CAS ]
  • 2
  • [ 22929-52-8 ]
  • [ 3761-92-0 ]
  • 3-Hexyl-tetrahydro-furan-3-ol [ No CAS ]
  • 3
  • [ 22929-52-8 ]
  • [ 6393-56-2 ]
  • 3-Pentyl-tetrahydro-furan-3-ol [ No CAS ]
  • 4
  • [ 22929-52-8 ]
  • [ 4548-78-1 ]
  • 3-Isopentyl-tetrahydro-furan-3-ol [ No CAS ]
  • 5
  • [ 22929-52-8 ]
  • phenylmagnesium bromide [ No CAS ]
  • [ 102654-25-1 ]
  • 6
  • [ 22929-52-8 ]
  • [ 107-21-1 ]
  • [ 176-34-1 ]
YieldReaction ConditionsOperation in experiment
80% toluene-4-sulfonic acid; In benzene; for 17h;Heating / reflux; 1,4,7-Trioxaspiro[4.4]nonane. A mixture of intermediate 12 (15.79 g, 183.5 mmol), ethylene glycol (16.7 mL, 300 mmol) and cat. TsOH.H2O (100 mg) in benzene (100 mL) was heated at reflux using Dean-Stark trap. After 17 h, the reaction mixture was cooled, diluted with ether (150 mL), washed with sat. Na2CO3 and brine (50 mL each), dried (Na2SO4), filtered and concentrated to give yellow liquid. Distillation under reduced pressure afforded intermediate 13 as a yellow liquid (19.13 g, 80percent). 1H NMR (500 MHz, CDCl3) delta: 3.9.4 (2H, t, J=7.0 Hz), 3.94-3.90 (4H, m), 3.68 (2H, s), 2.09 (2H, t, J=7.0 Hz).
80% toluene-4-sulfonic acid; In benzene; for 17h;Heating / reflux; Intermediate 13l,4, 7~Trioxaspiro[4.4]nonane. A mixture of intermediate 12 (15.79 g, 183.5 mmol), ethylene glycol (16.7 mL, 300 mmol) and cat. TsOH*H2O (100 mg) in benzene (100 mL) was heated at reflux using Dean-Stark trap. After 17 h, the reaction mixture was cooled, diluted with ether (150 mL), washed with sat. Na2CO3 and brine (50 mL each), dried (Na2SO4), filtered and concentrated to give yellow liquid. Distillation under reduced pressure afforded intermediate 13 as a yellow liquid (19.13 g, 80percent). 1H NMR (500 MHz, CDCl3) delta: 3.9.4 (2H, t, J = 7.0 Hz), 3.94- 3.90 (4H, m), 3.68 (2H, s), 2.09 (2H, t, J = 7.0 Hz).
80% toluene-4-sulfonic acid; In benzene; for 17h;Heating / reflux; 1,4,7-Trioxaspiro[4.4]nonane. A mixture of ethyl 3'-hydroxy-4'-oxo-6',7'-dihydro-4'H-spiro[cyclopentane-1,9'-pyrimido[2,1-c][1,4]oxazine]-2'-carboxylate (15.79 g, 183.5 mmol), ethylene glycol (16.7 mL, 300 mmol) and cat. TsOH.H2O (100 mg) in benzene (100 mL) was heated at reflux using Dean-Stark trap. After 17 h, the reaction mixture was cooled, diluted with ether (150 mL), washed with sat. Na2CO3 and brine (50 mL each), dried (Na2SO4), filtered and concentrated to give yellow liquid. Distillation under reduced pressure afforded the title compound as a yellow liquid (19.13 g, 80percent). 1H NMR (500 MHz, CDCl3) delta: 3.9.4 (2H, t, J=7.0 Hz), 3.94-3.90 (4H, m), 3.68 (2H, s), 2.09 (2H, t, J=7.0 Hz).
  • 7
  • [ 22929-52-8 ]
  • [ 540-63-6 ]
  • [ 176-40-9 ]
  • 8
  • [ 22929-52-8 ]
  • [ 79-19-6 ]
  • dihydro-furan-3-one thiosemicarbazone [ No CAS ]
  • 9
  • [ 22929-52-8 ]
  • [ 122-51-0 ]
  • [ 26118-20-7 ]
  • 10
  • [ 22929-52-8 ]
  • [ 119-26-6 ]
  • [ 3187-96-0 ]
  • 11
  • [ 22929-52-8 ]
  • [ 4294-57-9 ]
  • 3-<i>p</i>-Tolyl-tetrahydro-furan-3-ol [ No CAS ]
  • 12
  • [ 22929-52-8 ]
  • [ 75-08-1 ]
  • 3,3-bis-ethylmercapto-tetrahydro-furan [ No CAS ]
  • 14
  • [ 22929-52-8 ]
  • [ 18487-74-6 ]
  • 17
  • [ 453-20-3 ]
  • [ 22929-52-8 ]
YieldReaction ConditionsOperation in experiment
95% With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid; In dichloromethane; at -5 - 20℃; for 1h; To a 1 L flask, 3-tetrahydrofuran (3-OH-THF, 60.6 g, 0.68 mol, 1 equ.) was charged, followed by DCM (620 mL) and TEMPO(1.08 g, 0.0069 mol, 0.01 equ.) The solution was cooled to -5 °C. To which TCCA (159.6 g, 0.68 mol, 1 equ.) was added in portions controlling the tern- perature around -5 °C to 0 °C. The resulting mixture was allowed to warm to rt and monitored by GC-MS, Reaction was finished in 1 h to give 95percent yield (GC areapercent).
95% With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid; In dichloromethane; at -5 - 20℃; for 1h; To a 1 L flask, 3-tetrahydrofuran (3-OH-THF, 60.6 g, 0.68 mol, 1 equ.) was charged, followed by DCM (620 mL) and TEMPO(1.08 g, 0.0069 mol, 0.01 equ.) The solution was cooled to -5 °C. To which TCCA (159.6 g, 0.68 mol, 1 equ.) was added in portions controlling the tern- perature around -5 °C to 0 °C. The resulting mixture was allowed to warm to rt and monitored by GC-MS, Reaction was finished in 1 h to give 95percent yield (GC areapercent).
95% With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid; In dichloromethane; at -5 - 20℃; for 1h; To a 1 L flask, 3-tetrahydrofuran (3-OH-THF, 60.6 g, 0.68 mol, 1 equ.) was charged, followed by DCM (620 mL) and TEMPO(1.08 g, 0.0069 mol, 0.01 equ.) The solution was cooled to -5 °C. To which TCCA (159.6 g, 0.68 mol, 1 equ.) was added in portions controlling the tern- perature around -5 °C to 0 °C. The resulting mixture was allowed to warm to rt and monitored by GC-MS, Reaction was finished in 1 h to give 95percent yield (GC areapercent).
79% With pyridinium chlorochromate; In dichloromethane; at 20℃; Description 20 : Dihydro-3(2H)-furanone; A mixture of 3-hydroxytetrahydrofuran (3.0 g, 0.034 mol) and pyridinium chlorochromate (14.7 g, 0.068 mol) in DCM (100 ml) was stirred at room temperature overnight. The title product was obtained by pouring the crude product through a silica pad using ethyl acetate as the eluent. The title product was obtained from 2 elutions (2.29 g; 79percent). 1H NMR (CDCI3) delta: 2.50 (2H, t), 3.87 (2H, s), 4.26 (2H, t).
60% With acetic acid; pyridinium chlorochromate; In dichloromethane; at 20℃;Molecular sieve; Inert atmosphere; Pyridinium chlorochromate (6.5 g, 30 mmol, 1.5 equiv) was dissolved in 100 ml DCM at rt. Tetrahydro-3-furanol (1.6 ml, 20 mmol, 1 equiv) was added dropwise. 4 A molecular sieves (16 g) and glacial acetic acid (2 ml) were respectively added. The reaction mixture was stirred at rt overnight. A generous amount of Celite ® 545 was added and the solvent was removed by reduced pressure. The residue was then passed through a Celite ® 545 plug (10percent dichloromethane/diethyl ether) and the solvent was removed in vacuo. The residue was then purified by flash column chromatography (10percent dichloromethane/diethyl ether) to afford 3.45 (60percent yield). Spectral data correspond to that reported.24 1H NMR (400 MHz, CDCI3): delta 4.24 (t, J = 7.3 Hz, 2 H), 3.86 (s, 2 H), 2.48 (t, J = 7.3 Hz, 2 H).
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 3.5h; Pyridinium chlorochromate (85.8 g, 3.5 eq) was added in portions over a period of 5 minutes to a solution of 3-hydroxytetrahydrofuran (10.02 g, 1.0 eq) in dichloromethane (115 mL). The reaction mixture was stirred at ambient temperature for 3.5 hours and then applied directly to a column of silica gel (325 g). The column was eluted with diethyl ether. The fractions containing product were combined and the solvent was removed by atmospheric distillation to provide 5.22 g of tetrahydrofuran-3-one
With pyridinium chlorochromate; In dichloromethane; at 40℃; for 16h; 00182] Step 2: To a solution of tetrahydrofuran-3-ol (92.5 g, 1.05 mol) indichloromethane (2000 mL) was added pyridinium chlorochromate (454 g, 2.10 mol) and silicon gel (500 g). The reaction mixture was heated to 40°C. After 16 hours, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to afford the crude residue. The residue was purified via chromatography on silica gel (methanol/DCM, linear gradient) to afford dihydrofuran-3(2H)-one.
With silica gel; pyridinium chlorochromate; In dichloromethane; at 40℃; for 16h; To a solution of tetrahydrofuran-3-ol (92.5 g, 1.05 mol) indichloromethane (2000 mL) was added pyridinium chlorochromate (454 g, 2.10 mol) and silica gel (500 g). The reaction mixture was heated to 40°C. After 16 hours, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to afford the crude residue. The residue was purified via chromatography on silica gel (methanol/DCM, linear gradient) to afford dihydrofuran-3(2H)-one.
With pyridinium chlorochromate; In dichloromethane; at 0 - 20℃; b) dihydrofuran-3(2H)-one To a stirred solution of tetrahydrofuran-3-ol (3.0 g, 34 mmol) as obtained in step a) in DCM (60 mL) was added pyridiniumchloro chromate (14.65 g, 68 mmol) at 0 °C and the reaction mixture was stirred at rt for 16 h. Once the starting material was consumed (monitored by TLC), the reaction mixture was filtered through celite and the filtrate was washed with water, brine, drier over anhydrous Na2S04 and concentrated. The crude product (2.5 g) was used in the next step without further purification.
With tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide; In dichloromethane; at 20℃; for 2h;Molecular sieve; Tetrapropylammonium perruthenate (TPAP, 20 mg, 0.057 mmol) was added to a mixture of tetrahydrofuran-3-ol (616 mg, 7.0 mmol), N-methylmorphorine N-oxide (NMO, 11 mmol), activated molecular sieve powder (3.5 g) in dichloromethane (30 mL) at room temperature, the reaction mixture was stirred at room temperature for 2 h, then filtered through a short pad of Celite under reduced pressure. The EPO <DP n="85"/>dichloromethane solution ( 20 mL) of dihydrofuran-3(2H)-one was used as a stock solution (0.3 M).

  • 18
  • [ 110-91-8 ]
  • [ 22929-52-8 ]
  • [ 50603-71-9 ]
  • [ 106183-65-7 ]
  • [ 106183-66-8 ]
  • 19
  • [ 110-91-8 ]
  • [ 22929-52-8 ]
  • [ 106183-61-3 ]
  • [ 106183-62-4 ]
  • 20
  • [ 110-91-8 ]
  • [ 22929-52-8 ]
  • [ 118459-06-6 ]
  • [ 118459-09-9 ]
  • 21
  • [ 22929-52-8 ]
  • [ 917-64-6 ]
  • [ 64360-69-6 ]
  • 22
  • [ 22929-52-8 ]
  • [ 75-97-8 ]
  • (+/-)-1-(1-hydroxy-3-oxacyclopentyl)-3,3-dimethyl-2-butanone [ No CAS ]
  • 23
  • [ 22929-52-8 ]
  • [ 118459-16-8 ]
  • [ 118459-06-6 ]
  • [ 118459-09-9 ]
  • 24
  • [ 22929-52-8 ]
  • [ 118459-17-9 ]
  • [ 118459-07-7 ]
  • 25
  • [ 22929-52-8 ]
  • [ 118459-18-0 ]
  • [ 118459-08-8 ]
  • 26
  • [ 22929-52-8 ]
  • [ 130722-33-7 ]
  • [ 130722-40-6 ]
  • 27
  • [ 22929-52-8 ]
  • [ 137-07-5 ]
  • C10H11NOS [ No CAS ]
  • 28
  • [ 22929-52-8 ]
  • [ 74-86-2 ]
  • [ 137344-86-6 ]
  • 29
  • [ 22929-52-8 ]
  • [ 506-59-2 ]
  • [ 151-50-8 ]
  • [ 176445-75-3 ]
  • 30
  • [ 22929-52-8 ]
  • [ 151-50-8 ]
  • [ 506-87-6 ]
  • [ 81866-98-0 ]
YieldReaction ConditionsOperation in experiment
85-105% Dihydro-3(2H)-furanone (18, 24-28), (1.0 eq) was dissolved in a mixture of ethanol/water (7:1 v/v, 10 mL per mmole compound) containing sodium acetate trihydrate (1.5 eq). 4-[[(hydrazinocarbonyl)amino]methyl]-cyclohexanecarboxylic acid trifluoro acetate (mw 329.3, 1.0 eq) (see Murphy, A. M., et al, J. Am. Chem. Soc, 114, 3156-3157, 1992) was added and the mixture heated under reflux for 2 hrs. The mixture was then cooled, poured into dichloromethane (100 mL per mmole compound) and water (100 mL) added. The organic layer was separated, backwashed with saturated brine (100 mL). The organic layer was dried (Na2SO4), filtered and evaporated in vacuo to yield a white solid. Yield 85-105percent crude weight. Constructs (29-34) were used without further purification
Step E Cleavage A mixture of 7:2:1 TFA/CH2Cl2/H2O was added to the above resin. After 2 hours, the mixture was filtered and the resin was further washed with CH2Cl2. Removal of the solvent afforded the desired tetrahydrofuran-3-one.
  • 32
  • (+-)-tetrahydro-furan-3-ol [ No CAS ]
  • [ 22929-52-8 ]
  • 33
  • [ 1191-99-7 ]
  • [ 22929-52-8 ]
  • [ 1120-74-7 ]
  • (2R,3R)-3-chlorotetrahydrofuran-2-ol [ No CAS ]
  • 2-chloro-3-hydroxytetrahydrofuran [ No CAS ]
  • 34
  • [ 22929-52-8 ]
  • [ 75-75-2 ]
  • [ 627-27-0 ]
  • [ 503551-88-0 ]
  • 35
  • [ 1708-29-8 ]
  • [ 22929-52-8 ]
  • 36
  • [ 22929-52-8 ]
  • [ 74-90-8 ]
  • (R)-3-hydroxytetrahydrofuran-3-carbonitrile [ No CAS ]
  • (S)-3-hydroxytetrahydrofuran-3-carbonitrile [ No CAS ]
  • 37
  • [ 22929-52-8 ]
  • [ 74-90-8 ]
  • 3-hydroxytetrahydrofuran-3-carbonitrile [ No CAS ]
  • 38
  • [ 22929-52-8 ]
  • [ 13078-80-3 ]
  • C12H14ClNO [ No CAS ]
  • 39
  • [ 1191-99-7 ]
  • [ 22929-52-8 ]
  • [ 20245-14-1 ]
  • trans-3-bromo-2-hydroxytetrahydrofuran [ No CAS ]
  • 40
  • [ 22929-52-8 ]
  • [ 95-92-1 ]
  • C8H10O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
5% With sodium; In ethanol; at 20℃; General procedure: Similar to as described in General Procedure Y Step 1, diethyl oxalate was reacted withoxolan-3-one to give 400 mg (5percent) of ethyl 2-oxo-2-(4-oxooxolan-3-yl)acetate as yellow oil..; Step 1: A solution of cycloalkylketone (1.0 eq.) in EtOH (0.5 mL/mmol) was cooled to 0 °C, then sodium ethoxide (21percent wt solution in EtOH, 1.1 eq.) was added. To this mixture was added diethyl oxylate (1.0 eq.) and the mixture was allowed to warm to room temperature overnight. In vacuo concentration provided the desired product of sufficient purity to be used directly (yield assumed to be quantitative).
  • 41
  • [ 22929-52-8 ]
  • [ 865869-67-6 ]
  • [ 1036969-36-4 ]
YieldReaction ConditionsOperation in experiment
With trans-4-methylcyclohexanecarbonyl chloride; triethylamine; In dichloromethane; at 45℃; for 32h; Intermediate 164 Ethyl 3-[[(trans-4-methylcyclohexyl)carbonyl](tetrahydro-3-furanyl)amino]-1- (phenylmethyl)-1 ate To a solution of Intermediate 163 (3.73 g, 11.8 mmol) in DCM (35 mL) was added trans-4- methylcyclohexanecarbonyl chloride (2.28 g, 14 mmol), followed by triethylamine (2.5 mL). The reaction was heated at 45 °C for 16 hours under nitrogen, whereupon further aliquots of triethylamine (2 mL) and trans-4-methylcyclohexanecarbonyl chloride (1.5 g) were added. Heating was continued for a further 16 hours. After cooling, the mixture was diluted with DCM, washed with hydrochloric acid solution (1M), then water, and then saturated sodium bicarbonate solution. The organic layer was passed through a hydrophobic frit, evaporated, and purified using 120 g ISCO Flash column, eluting with a gradient of ethyl acetate in cyclohexane (5-100percent) to give the title compound. MS calcd for (C25H33N304+ H) + : 440 MS found (electrospray) : (M+H) += 440
  • 42
  • [ 22929-52-8 ]
  • [ 21377-11-7 ]
  • [ 865869-67-6 ]
YieldReaction ConditionsOperation in experiment
With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; for 16h; Intermediate 163 Ethyl 1-(phenylmethyl)-3-[(tetrahydro-3-furanyl)amino]-1H-pyrazole-4-carboxylate. To a solution of ethyl 3-amino-1-(phenylmethyl)-1H-pyrazole-4-carboxylate (7.88 g, 32 mmol) and dihydro-3 (2H)-furanone (1.60 g, 18.6 mmol) in DCM (100 mL) was added sodium triacetoxyborohydride (7.88 g, 37 mmol) and acetic acid (3.2 mL). The mixture was stirred for 16 hours, partitioned between DCM and saturated sodium bicarbonate solution and applied through a hydrophobic frit. The organic fraction was evaporated, the residue purified using a 330 g ISCO Flash column, eluting with a gradient of ethyl acetate in cyclohexane (5- 60percent) to give the title compound. MS calcd for (C17H21N303+ H) + : 316 MS found (electrospray) : (M+H) += 316
  • 43
  • [ 29212-66-6 ]
  • [ 22929-52-8 ]
YieldReaction ConditionsOperation in experiment
67% Dihydrofuran-3(2H)-one. A mixture of 3-hydroxyfuran (24 g, 272 mmol) and TEMPO (0.86 g, 5.5 mmol) in CH2Cl2 (175 mL) and KBr (7.141 g, 60 mmol) in water was vigorously stirred and cooled in an ice-water bath. The pH of NaOCl (commercial grade bleach, 600 mL, 806 mmol) was adjusted to 9.5 by dissolving NaHCO3 (8.632 g, 102.75 mmol) immediately before use. This NaOCl solution was added over 40 min while keeping the internal temperature of the reaction mixture between 0° C. and 5° C. After 2 h, the greenish-yellow organic phase was separated and aqueous phase was saturated with NaCl and extracted with CH2Cl2 (4.x.100 mL). The combined organic phases was washed with 10percent HCl aq. (1.x.300 mL) containing KI (12 g) and 10percent aq. Na2CO3 (2.x.150 mL). The organic layer dried (Na2SO4), filtered and concentrated to give intermediate 12 as a pale yellow liquid (15.79 g, 67percent) which was used without purification. 1H NMR (500 MHz, CDCl3) delta: 4.24 (2H, t, J=7.3 Hz), 3.86 (2H, s), 2.49 (2H, t, J=7.3 Hz).
67% With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide; In dichloromethane; at 0 - 5℃; for 2.66667h;pH 9.5; Intermediate 12Dihydrofuran-3(2H)-one . A mixture of 3-hydroxyfuran (24 g, 272 mmol) and TEMPO (0.86 g, 5.5 mmol) in CH2Cl2 (175 mL) and KBr (7.141 g, 60 mmol) in water was vigorously stirred and cooled in an ice- water bath. The pH of NaOCl (commercial grade bleach, 600 mL, 806 mmol) was adjusted to 9.5 by dissolving NaHCO3 (8.632 g, 102.75 mmol) immediately before use. This NaOCl solution was added over 40 min while keeping the internal temperature of the reaction mixture between 0 0C and 5 °C. After 2 h, the greenish-yellow organic phase was separated and aqueous phase was saturated with NaCl and extracted with CH2Cl2 (4 X 100 mL). The combined organic phases was washed with 10percent HCl aq. (1 X 300 mL) containing KI (12 g) and 10percent aq. Na2CO3 (2 X 150 mL). The organic layer dried (Na2SO4), filtered and concentrated to give intermediate 12 as a pale yellow liquid <n="47"/>(15.79 g, 67percent) which was used without purification. 1H NMR (500 MHz, CDCl3) delta: 4.24 (2H, t, J = 7.3 Hz), 3.86 (2H, s), 2.49 (2H, t, J = 7.3 Hz).
67% With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide; In dichloromethane; water; at 0 - 5℃; for 2.66667h;pH 9.5; Dihydrofuran-3(2H)-one. A mixture of 3-hydroxyfuran (24 g, 272 mmol) and TEMPO (0.86 g, 5.5 mmol) in CH2Cl2 (175 mL) and KBr (7.141 g, 60 mmol) in water was vigorously stirred and cooled in an ice-water bath. The pH of NaOCl (commercial grade bleach, 600 mL, 806 mmol) was adjusted to 9.5 by dissolving NaHCO3 (8.632 g, 102.75 mmol) immediately before use. This NaOCl solution was added over 40 min while keeping the internal temperature of the reaction mixture between 0° C. and 5° C. After 2 h, the greenish-yellow organic phase was separated and aqueous phase was saturated with NaCl and extracted with CH2Cl2 (4.x.100 mL). The combined organic phases were washed with 10percent HCl aq. (1.x.300 mL) containing KI (12 g) and 10percent aq. Na2CO3 (2.x.150 mL). The organic layer dried (Na2SO4), filtered and concentrated to give the title compound as a pale yellow liquid (15.79 g, 67). 1H NMR (500 MHz, CDCl3) delta: 4.24 (2H, t, J=7.3 Hz), 3.86 (2H, s), 2.49 (2H, t, J=7.3 Hz).
  • 44
  • [ 57595-23-0 ]
  • [ 22929-52-8 ]
YieldReaction ConditionsOperation in experiment
6.8 g (79%) In sulfuric acid; (b) Tetrahydrofuran-3-one A solution of <strong>[57595-23-0]methyl 3-oxo-tetrahydrofuranyl-4-carboxylate</strong> (14.5 g, 0.1 mol) in 10percent H2 SO4 (50 ml) was refluxed for 1 hour. The reaction mixture was cooled and extracted with ether (3*100 ml). The organic layers were combined, dried over MgSO4 and concentrated in vacuo. The pale gold residue was distilled to afford 6.8 g (79percent) of tetrahydrofuran-3-one, B.P. 74°-75° C. at 100 mm Hg.
  • 45
  • [ 22929-52-8 ]
  • [ 75-09-2 ]
  • [ 64360-69-6 ]
YieldReaction ConditionsOperation in experiment
With methyl magnesium iodide; In methanol; diethyl ether; A. Methyl magnesium iodide (3.0M in Et2 O, 20 mL) was added to a solution of <strong>[22929-52-8]tetrahydrofuran-3-one</strong> (1.6 g, 18.6 mmol) in 15 mL of Et2 O at 0° C. After stirring 4 h at 0° C. the mixture was quenched with sat. aq. NH4 Cl solution and extracted with Et2 O. The combined extracts were dried over MgSO4 and concentrated under reduced pressure to give the crude material. Purification by chromatography (CH2 Cl2 to 1percent MeOH/CH2 Cl2 to 2percent MeOH/CH2 Cl2) gave 3-hydroxy-3-methyltetrahydrofuran (0.290 g). 1 H NMR consistent with structure.
  • 46
  • [ 22929-52-8 ]
  • 1-ethenyl-3-oxacyclopentanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
(a) 3-Hydroxy-3-vinyltetrahydrofuran Obtained from <strong>[22929-52-8]tetrahydrofuran-3-one</strong> (J. Org. Chem., 1989, 54, 1249) and vinylmagnesium bromide, by a procedure similar to that described in Example 5(a), as an oil. Rf 0.45 (SS 7). delta(CDCl3): 1.90 (1H, br s), 1.92-2.20 (2H, m), 3.62-3.78 (2H, m), 3.92-4.10 (2H, m), 5.20 (1H, d), 5.44 (1H, d), 5.95-6.08 (1H, dd). HRMS: m/z 114.068.
  • 47
  • [ 22929-52-8 ]
  • [ 81866-98-0 ]
YieldReaction ConditionsOperation in experiment
With ammonium carbonate; In ethanol; water; EXAMPLE 1 7-Oxa-1,3-diazaspiro[4.4]nonane-2,4-dione STR8 A solution of 19.2 g of ammonium carbonate in 42 ml of ethanol and 28 ml of water is added to 10.0 g of 3-ketotetrahydrofuran. The resulting mixture is heated to 55° and to it is then added, dropwise, a solution of 6.3 g of potassium cyanide in 15 ml of water. The reaction mixture is stirred at 55° for 18 hrs. Thereafter the reaction mixture is evaporated in vacuo to dryness to obtain a residue. The residue is dissolved in a minimum of water and the mixture made acidic with 2 N hydrochloric acid. The first crop of the title product precipitates out on cooling and is filtered off. A second crop of the title product is obtained by concentrating the filtrate and cooling. The two combined crops are recrystallized from ethanol to give refined title product, m.p. 202°-204°.
  • 48
  • [ 22929-52-8 ]
  • (carbethoxymethyene)triphenylphosphorane [ No CAS ]
  • [ 138498-96-1 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; LiOH; In ethanol; acetonitrile; EXAMPLE 25 Preparation of (4,5-dihydro-3(2H)-furylidene)acetic acid A mixture of 3.9 g of <strong>[22929-52-8]tetrahydrofuran-3-one</strong> and 22 g of (carbethoxymethyene)triphenylphosphorane in 40 mL of anhydrous acetonitrile was heated to reflux for 4 days. After concentration, the residue was purified by chromatography on silica gel. Elution with 25percent ethyl acetate in hexanes gave, after evaporative distillation at 15 mm (oven temperature 140°C), 3.6 g of product as a fragrant liquid. The ester was saponified in 20 mL of ethanol with 20 mL of 1N LiOH for 24 hours. After acidification with 6N HCl to pH2, the acid was isolated by concentration to dryness and extraction with methylene chloride. Azeotropic drying with toluene gave 3.1 g of product as a resinous solid.
  • 49
  • [ 22929-52-8 ]
  • C4H7NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
With ammonia; acetic acid; In methanol; at 0 - 25℃; for 0.25h; Preparation of (S)-3-amino-tetrahydrofuran-3-carboxylic acid n-butyl ester via chemical resolution with L-mandelic acidTo a solution of dihydrofuran-3-one (10.0 g, 116.2 mmol) in MeOH (50 ml_) was added a solution of 7 N NH3/MeOH (33 ml_) at ambient temperature. Themixture was cooled to 0 °C and 7.66 g of AcOH was added over 5 min whilemaintaining the temperature below 25 °C. The mixture was stirred at ambienttemperature for 10 min and 5.64 g of NaCN was added in one portion. Themixture was heated to 50 °C, stirred for 2 h and then concentrated to removethe MeOH and ammonia. EtOAc (40 ml_) was added to the concentrated mixture and then stirred for 15 min. The slurry was filtered and the wet cake was washed twice with 20 ml_ EtOAc. The combined filtrates, containing the desired S-amino-tetrahydrofuran-S-carbonitrile, were concentrated and to theresidue was added 20 ml_ of n-BuOH. The resulting mixture was cooled to 0 °C <n="95"/>and then 100 ml_ of 5.5 N HCI in n-BuOH was added. The resulting mixture was stirred at ambient temperature for 12 h.The mixture was cooled to 0 °C and 20 ml_ water was added. The mixture wasthen concentrated to remove most of the n-BuOH. Saturated NaHCO3 was added to the residue to pH>7 and the resulting mixture was extracted twice with 200 ml_ of 2-methyltetrahydrofuran. The organic extracts were washed once with brine (80 ml_) and then concentrated to give 18.3 g of the title compound (85percent overall yield). 1H NMR (CDCI3, ppm): 2.02 (s, 2H), 2.09-2.15 (m, 1 H), 2.43-2.50 (m ,1 H), 3.75-3.78 (d, J=9.04, 1 H), 3.98-4.08 (m, 3H). 13C NMR (CDCI3, ppm) 40.80, 54.03, 67.51 , 78.72, 122.63.
  • 50
  • [ 22929-52-8 ]
  • [ 950651-22-6 ]
  • [ 1044507-03-0 ]
YieldReaction ConditionsOperation in experiment
With H-Y Zeolites; In methanol;Heating / reflux; Description 20: 3-(4-Bromophenyl)-7-oxa-1 ,4-diazaspiro[4.4]nonan-2-one; A mixture of <strong>[22929-52-8]dihydro-3(2H)-furanone</strong> (0.951 g) and 2-amino-2-(4-bromophenyl)acetamide(D17) (2.3g) and H-Y Zeolites (2.3g) in methanol (125ml) was refluxed under argon overnight. The mixture was filtered through Kieselgugr and the solvent was removed to give the title compound as an off white solid foam (2.59g) which was used without further purification.Mass spectrum Found 297/9 (MH+).
With H-Y Zeolites; In methanol;Heating / reflux; A mixture of <strong>[22929-52-8]dihydro-3(2H)-furanone</strong> (0.951 g) and 2-amino-2-(4-bromophenyl)acetamide(D1 ) (2.3g) and H-Y Zeolites (2.3g) in methanol (125ml) was refluxed under argon overnight. The mixture was filtered through Kieselguhr and the solvent was removed to give the title compound as an off white solid foam (2.59g), which was used without further purification.Mass spectrum Found 297/9 (MH+).
  • 51
  • [ 22929-52-8 ]
  • [ 22288-78-4 ]
  • [ 1019338-15-8 ]
YieldReaction ConditionsOperation in experiment
Methyl 3-amino-2-thiophenecarboxylate (3.8 g), <strong>[22929-52-8]dihydro-3(2H)-furanone</strong> (2.5 g) and glacial acetic acid (4.4 g) were dissolved in DCM (75 ml_). Sodium triacetoxyborohydride (12.6 g) was added portion-wise and the reaction was stirred at room temperature over a weekend.Water (70 ml.) was added and the reaction mixture was neutralised by the addition of solid sodium bicarbonate. The organics were separated, dried by passing through a hydrophobic frit and evaporated in vacuo. The crude material was purified by ISCO Companion silica chromatography, eluting with a gradient 5-100percent EtOAc in cyclohexane to give the title compound.MS calcd for (Ci0H13NO3S + H)+: 228MS found (electrospray): (M+H)+ = 228
  • 52
  • [ 22929-52-8 ]
  • [ 109-73-9 ]
  • C8H15NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
In acetonitrile; at 20℃;Molecular sieve; To a solution of <strong>[22929-52-8]dihydrofuran-3(2H)-one</strong> (0.5 g, 6.0 mmol, Small Molecules Inc.) in acetonitrile (10 mL) were added molecular sieves (0.5 g) and butan-1-amine (0.4 g, 5.5 mmol, Aldrich). The reaction mixture was stirred at room temperature overnight and then filtered. To the filtrate was added potassium thiocyanate (0.7 g, 7.3 mmol, Aldrich). The temperature was adjusted to 50° C. and the mixture was stirred until the solids were dissolved. Then, iodine (2.8 g, 10.9 mmol, EMD Chemicals) was added to the mixture and stirred at 50° C. overnight. The reaction mixture was cooled, concentrated and dissolved in EtOAc (15 mL). The solution was washed with Na-meta-bisulfite 20percent (15 mL) by mixing the layers for 30 minutes. The organic layer was washed twice with 1N HCl (15 mL). The aqueous layers (metabisulfite and HCl) were combined and the pH was adjusted to pH ~9 by adding NH4OH. The product was extracted with EtOAc (4*20 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated to obtain the crude product (0.22 g) of the title compound. MS (ESI+) m/z 199 (M+H)+.
  • 53
  • [ 22929-52-8 ]
  • [ 1089706-28-4 ]
  • 6-bromo-8-fluoro-2,2-tetrahydrospirofuranylchroman-4-one [ No CAS ]
  • 6-bromo-8-fluoro-2,2-tetrahydrospirofuranylchroman-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyrrolidine; In acetonitrile; at 60℃; for 0.333333h;Microwave irradiation; l-(5-Bromo-3-fluoro-2-hydroxyphenyl)ethanone (0.200 g, 0.858 mmol), dihydrofuran- 3(2H)-one (0.222 g, 2.57 mmol), and pyrrolidine (0.142 ml, 1.72 mmol) were dissolved in MeCN (0.5 mL) and heated in the microwave for 20 minutes fixed at 60 0C. After cooling, the reaction was diluted with EtOAc and washed with IN HCl. The aqueous layer was extracted with EtOAc. The organic layers were combined, washed with water, brine, dried over sodium sulfate, and concentrated. The crude product was purified by silica gel chromatography (1 :4 EtOAc/hexanes) to afford the titled products. MS m/z: 301.0 (100percent, M).
  • 54
  • [ 22929-52-8 ]
  • [ 613-94-5 ]
  • N'-[(Z)-dihydrofuran-3(2H)-ylidene]benzoylhydrazide [ No CAS ]
  • N'-[(E)-dihydrofuran-3(2H)-ylidene]benzoylhydrazide [ No CAS ]
 

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Technical Information

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