Home Cart Sign in  
Chemical Structure| 163457-23-6 Chemical Structure| 163457-23-6

Structure of 3,3-Difluoropyrrolidine HCl
CAS No.: 163457-23-6

Chemical Structure| 163457-23-6

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

Synonyms: 3,3-Difluoropyrrolidine hydrochloride

4.5 *For Research Use Only !

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

Change View

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

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 163457-23-6 ]

CAS No. :163457-23-6
Formula : C4H8ClF2N
M.W : 143.56
SMILES Code : FC1(F)CNCC1.[H]Cl
Synonyms :
3,3-Difluoropyrrolidine hydrochloride
MDL No. :MFCD03788948
InChI Key :YYVPZQADFREIFR-UHFFFAOYSA-N
Pubchem ID :24903482

Safety of [ 163457-23-6 ]

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

Computational Chemistry of [ 163457-23-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 33.05
TPSA ?

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

12.03 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

1.4
Log Po/w (WLOGP)?

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

1.88
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.

1.14
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

1.77
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.24

Water Solubility

Log S (ESOL):?

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

-1.61
Solubility 3.51 mg/ml ; 0.0244 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.

-1.26
Solubility 7.95 mg/ml ; 0.0554 mol/l
Class?

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

Very 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

-1.52
Solubility 4.34 mg/ml ; 0.0302 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

Yes
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.

-6.18 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

3.0
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)

1.15

Application In Synthesis of [ 163457-23-6 ]

* 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.

  • Downstream synthetic route of [ 163457-23-6 ]

[ 163457-23-6 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 195447-25-7 ]
  • [ 163457-23-6 ]
YieldReaction ConditionsOperation in experiment
100% With hydrogenchloride; In 1,4-dioxane; at 0 - 20℃; for 1.66667h; [0358] Part C: To a solution of 1,1-dimethylethyl 3,3-difluoropyrrolidine-1-carboxylate (0.868 g, 4.19 mmol) in 1.5 mL of 1,4-dioxane was added a solution of hydrogen chloride in 1,4-dioxane (4 M, 11 mL, 44 mmol) at 0 C. The mixture was stirred at 0 C. for 40 min, at room temperature for 1 h and was then concentrated to afford 0.65 g (100%) of 3,3-difluoropyrrolidine hydrochloride: 1H-NMR (CD3OD) δ 3.54 (2H, t, J=11.9 Hz), 3.43 (2H, t, J=7.8 Hz), 2.40 (2H, m).
100% With hydrogenchloride; In 1,4-dioxane; for 2.0h; To a stirred solution of <strong>[195447-25-7]tert-butyl 3,3-difluoropyrrolidine-1-carboxylate</strong> (step 2, 1.61 g, 7.77 mmol) in dioxane (15 ml), was added 6N HCl in dioxane (20 ml) and stirred for about 2 hours. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated under reduced pressure to afford the desired product (1.11 g, yield: 100%). Next reaction was carried out without any further purification.
With hydrogenchloride; In 1,4-dioxane; for 0.2h; To a stirred solution of tert-butyl 3,3-difluoropyrrolidine-l-carboxylate (step 2, 1.61 g, 7.77 mmol) in dioxane (15 ml), was added 6N HCl in dioxane (20 ml) and stirred for about 2 hours. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated under reduced pressure to afford the desired product (1.11 g, yield: 100%). Next reaction was carried out without any further purification.
4.1 g With hydrogenchloride; In water; DAST (4.03 g, 67.6 mmol, 2.5 eq.) was added to a solution of tert-butyl 3- oxopyrrolidine-l-carboxylate (5 g, 27.0 mmol, 1.0 eq.) in dichloromethane (30 mL). The reaction was stirred for 5 hours at room temperature. The reaction mixture was poured into ice cold sat. NaHCCL solution (100 mL) and extracted with dichloromethane for three times. The organic extracts were combined, washed with brine, dried over anhydrous sodium sulfate, and concentrated to give crude Boc-3,3-difluoropyrrolidine (5.9 g, quantitative yield), which was then treated with 6 N HC1 in dioxane to give 3,3-difluoropyrrolidine hydrochloride (4.1 g, quantitative yield). LC-MS m/z [M+H]+ calc’d for C4H8CIF2N, 110; found, 110.

  • 2
  • [ 132898-96-5 ]
  • [ 163457-23-6 ]
  • [ 1234339-94-6 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; dichloromethane; at -50 - 20℃; The hydrochloride salt of racemic 3-fluoropyrrolidinc (628 mg, 5mmol) was added to a solution of 2,3-oxoindohne-5-sulfonyl chloride (1.2 g, 4.9 mmol) and diisopropylethyl amine (2.6 mL, 15 mmol) in 1 :1 CH2Cl2ZTHF (50 mL) at -50 C. The solution was warmed to room temperature and slirred at that temperature for 12 hours. The reaction mixture was concentrated, dissolved in CII2CI2. and then washed with saturated NaHCO3 and brine. I he organic layer was dried (MgSO4), filtered, concentrated, and purified by flash chromatography on silica gel (5% MeOH in CH2Cl2) to provide 1.4 g of the product as an orange solid
  • 3
  • [ 132898-96-5 ]
  • [ 163457-23-6 ]
  • [ 1234339-96-8 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; dichloromethane; at -50 - 20℃; T he hydrochloride salt of 3,3-difluoropyrrolidine (475 mg, 3,3 mmol) ^as added to a solution of2.3-dioxoiotando.me-5-suifonyl chloride (1 ,0 g, 4, 1 mmol) and diisopropyleth) 1 amine (2 0 ml, 12 mmol) in 1 : 1 CH2Cl2ZTHF (40 mL) at -50 C. The solution was warmed to room temperature and stirred at that temperature for 12 hours The reaction mixture was then concentrated, dissolved in CH2Cl2. and washed with saturated NaHCOj and brine. The organic layer was dried (MgSO4), filtered, concentrated, and purified by flash chromatography on silica gel (5% MeOH in CH2Cl2) to provide 575 mg of the product as an orange solid
  • 4
  • [ 22280-60-0 ]
  • [ 163457-23-6 ]
  • [ 1435954-09-8 ]
YieldReaction ConditionsOperation in experiment
47% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 4h; General procedure: To a solution of <strong>[22280-60-0]6-chloro-2-methyl-3-nitropyridine</strong> (0.3 g, 1.74 mmol) in DMF (2 mL) was added K2C03 (0.72 g, 5.23 mmol) followed by 3,3-difluoropyrrolidine hydrochloride (0.74 g, 5.23 mmol) and the reaction mixture was heated for 4 h at 80°C. The reaction mixture was then diluted with ethyl acetate and the organic layer was washed with saturated aqueous sodium bicarbonate solution. The organic layer was then dried over sodium sulphate and concentrated. The crude material obtained was purified by column chromatography (silica: 100-200 mesh, MeOH:DCM 2-3percent) to afford the title compound (0.2 g, 47percent). LCMS (ES+) 244.05 (M+H)+, RT 3.028 minutes (method 1).
47% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 4h; Intermediate 51 6-(3,3-Difluoropyrrolidin-1-yl)-2-methyl-3-nitropyridine [0271] To a solution of <strong>[22280-60-0]6-chloro-2-methyl-3-nitropyridine</strong> (0.3 g, 1.74 mmol) in DMF (2 mL) was added K2CO3 (0.72 g, 5.23 mmol) followed by 3,3-difluoropyrrolidine hydrochloride (0.74 g, 5.23 mmol) and the reaction mixture was heated for 4 h at 80° C. The reaction mixture was then diluted with ethyl acetate and the organic layer was washed with saturated aqueous sodium bicarbonate solution. The organic layer was then dried over sodium sulphate and concentrated. The crude material obtained was purified by column chromatography (silica: 100-200 mesh, MeOH: DCM 2-3percent) to afford the title compound (0.2 g, 47percent). LCMS (ES+) 244.05 (M+H)+, RT 3.028 minutes (method 1).
  • 5
  • [ 24424-99-5 ]
  • [ 163457-23-6 ]
  • [ 195447-25-7 ]
YieldReaction ConditionsOperation in experiment
89% With potassium carbonate; In methanol; at 20℃; Add 3,3-difluoropyrrolidine hydrochloride (3.52g, 24.50mmol) to a 100mL bottle and dissolve it in MeOH (51mL),Add K2CO3 (6.74g, 48.80mmol) under ice bath, stir evenly,Then slowly add di-tert-butyl dicarbonate (6.4mL, 28.00mmol) dropwise,Move to room temperature and react overnight. The insoluble matter was removed by filtration, diluted with water, extracted with EtOAc, combined the organic phases, washed with H2O and saturated NaCl solution, dried with anhydrous Na2SO4, concentrated under reduced pressure, and the concentrated solution was separated by silica gel column chromatography (eluent: PE/EtOAc( v/v)=1/10) to obtain a colorless transparent liquid (4.50g, 89%).
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 163457-23-6 ]

Fluorinated Building Blocks

Chemical Structure| 136725-53-6

A214432 [136725-53-6]

(S)-3-Fluoropyrrolidine hydrochloride

Similarity: 0.86

Chemical Structure| 169750-17-8

A278152 [169750-17-8]

3-Fluoropyrrolidine hydrochloride

Similarity: 0.86

Chemical Structure| 136725-55-8

A173142 [136725-55-8]

(R)-(-)-3-Fluoropyrrolidine Hydrochloride

Similarity: 0.86

Chemical Structure| 496807-97-7

A113721 [496807-97-7]

3,3-Difluoropiperidine hydrochloride

Similarity: 0.84

Chemical Structure| 144230-52-4

A331925 [144230-52-4]

4,4-Difluoropiperidine hydrochloride

Similarity: 0.80

Related Parent Nucleus of
[ 163457-23-6 ]

Pyrrolidines

Chemical Structure| 136725-53-6

A214432 [136725-53-6]

(S)-3-Fluoropyrrolidine hydrochloride

Similarity: 0.86

Chemical Structure| 169750-17-8

A278152 [169750-17-8]

3-Fluoropyrrolidine hydrochloride

Similarity: 0.86

Chemical Structure| 136725-55-8

A173142 [136725-55-8]

(R)-(-)-3-Fluoropyrrolidine Hydrochloride

Similarity: 0.86

Chemical Structure| 869481-94-7

A120803 [869481-94-7]

(3S,4R)-rel-3,4-Difluoropyrrolidine hydrochloride

Similarity: 0.80

Chemical Structure| 1780964-59-1

A243606 [1780964-59-1]

8,8-Difluoro-2-azaspiro[4.5]decane hydrochloride

Similarity: 0.69