[ CAS No. 5661-55-2 ] {[proInfo.proName]}

Name: 5661-55-2|4-Phenylazetidin-2-one|98%
Brand: Ambeed
SKU: A184350
Price: 42.0 USD
Availability: InStock
Rating: 95 (26 reviews)

,{[proInfo.pro_purity]}

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

2D 3D

Structure of 5661-55-2 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 5661-55-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 5661-55-2 ]

SDS Specification

Alternatived Products of [ 5661-55-2 ]

Product Details of [ 5661-55-2 ]

CAS No. :	5661-55-2	MDL No. :	MFCD02179052
Formula :	C₉H₉NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MWKMQPSNTJCASD-UHFFFAOYSA-N
M.W :	147.17	Pubchem ID :	568818
Synonyms :

Calculated chemistry of [ 5661-55-2 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	45.82
TPSA :	29.1 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.64 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.58
Log Po/w (XLOGP3) :	0.78
Log Po/w (WLOGP) :	0.54
Log Po/w (MLOGP) :	1.96
Log Po/w (SILICOS-IT) :	1.97
Consensus Log Po/w :	1.37

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.58
Solubility :	3.86 mg/ml ; 0.0262 mol/l
Class :	Very soluble
Log S (Ali) :	-0.97
Solubility :	15.7 mg/ml ; 0.107 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.92
Solubility :	0.179 mg/ml ; 0.00121 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.32

Safety of [ 5661-55-2 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 5661-55-2 ]

* 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 [ 5661-55-2 ]

[ 5661-55-2 ] Synthesis Path-Downstream 1~52

1
[ 292638-84-7 ]
[ 1189-71-5 ]
[ 5661-55-2 ]

Yield	Reaction Conditions	Operation in experiment
90%		N-Chlorosulfonyl isocyanate (0.846 g, 6 mmol,1.2 equiv) was added dropwise over 10 min to a solution ofstyrene (7) (0.520 g, 5 mmol, 1.0 equiv) in anhydrousdiethyl ether (5 ml) at room temperature under an inertatmosphere. The mixture was stirred at room temperaturefor 2 h, and the solvent was removed under reducedpressure. The residue was taken up in diethyl ether (10 ml)and added dropwise over 10 min to a vigorously stirredsolution of sodium carbonate (1.70 g, 16 mmol, 3.3 equiv)and sodium sulfite (0.882 g, 7 mmol, 1.4 equiv) in water(10 ml) containing ice (10 g). The solution was stirred for 1 hand filtered. The organic layer was separated, while theaqueous layer was extracted with diethyl ether (3×10 ml).The combined organic extracts were dried over anhydrousNa2SO4, filtered, and the solvent was evaporated underreduced pressure to yield 4-phenylazetidin-2-one (8) (0.662 g,4.5 mmol) in a very good yield (90%). The obtainedproduct was dissolved in anhydrous THF (20 ml), thentetrabutylammonium bromide (0.128 g, 0.4 mmol, 0.1 equiv),KOH (0.246 g, 4.4 mmol, 1.0 equiv), and MeI (0.852 g,6.0 mmol, 1.4 equiv) were added and the solution wasstirred for 8 h at 25C. The reaction mixture was filtered,the filtrate was poured into water and extracted with Et2O.The combined organic layers were dried over anhydrousNa2SO4 and evaporated under reduced pressure to yield0.507 g (70%) of 1-methyl-4-phenylazetidin-2-one (5j) aswhite solid. 1H NMR spectrum (400 MHz, CDCl3), delta, ppm(J, Hz): 2.73 (3H, t, J = 0.9); 2.79 (1H, ddd, J = 14.0, J = 2.3,J = 0.9); 3.35 (1H, ddd, J = 14.0, J = 5.1, J = 0.9); 4.46(1H, dd, J = 5.1, J = 2.3); 7.25-7.41 (5H, m). Intermediate5j was employed without further purification in thereduction reaction. LiAlH4 (0.319 g, 8.4 mmol, 3 equiv) wascarefully added to a solution of AlCl3 (1.11 g, 8.4 mmol,3 equiv) in dry diethyl ether (15 ml) at 0C. The reaction mixture was stirred for 10 min at 0C, then refluxed for 30 min.1-Methyl-4-phenylazetidin-2-one (5j) (0.451 g, 2.8 mmol,1 equiv) in dry diethyl ether (10 ml) was added slowly and,after the addition was complete, reflux was maintained for4 h. The reaction was cooled to room temperature and 5% aqueous NaOH solution (10 ml) was added carefully. Theaqueous phase was extracted with Et2O (3×10 ml), dried overanhydrous Na2SO4, and evaporated under reduced pressure.

Reference： [1]Chemical Communications,2014,vol. 50,p. 1698 - 1700
[2]Chemistry - A European Journal,2014,vol. 20,p. 12190 - 12200
[3]Chemical Communications,2015,vol. 51,p. 15588 - 15591
[4]Chemistry of Heterocyclic Compounds,2017,vol. 53,p. 329 - 334
Khim. Geterotsikl. Soedin.,2017,vol. 53,p. 329 - 334,6
[5]Tetrahedron Asymmetry,2001,vol. 12,p. 2351 - 2358
[6]Organic Letters,2012,vol. 14,p. 126 - 129
[7]Tetrahedron,2013,vol. 69,p. 1279 - 1284
[8]European Journal of Organic Chemistry,2015,vol. 2015,p. 1500 - 1506
[9]European Journal of Organic Chemistry,2014,vol. 2014,p. 6753 - 6760
[10]Tetrahedron Letters,1986,vol. 27,p. 5147 - 5150

2
[ 6940-78-9 ]
[ 5661-55-2 ]
[ 89044-72-4 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1983,p. 959 - 960
[2]Journal of the Chemical Society. Perkin transactions I,1993,p. 2027 - 2046

3
[ 111-24-0 ]
[ 5661-55-2 ]
[ 89044-74-6 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1993,p. 2027 - 2046
[2]Journal of the Chemical Society. Chemical communications,1983,p. 959 - 960

4
[ 5661-55-2 ]
[ 24443-15-0 ]
[ 154218-80-1 ]

Yield	Reaction Conditions	Operation in experiment
50%	With potassium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In tetrahydrofuran for 3h; Ambient temperature;

Reference： [1]Begley, Michael J.; Crombie, Leslie; Haigh, David; Jones, Raymond C. F.; Osborne, Steven; Webster, Richard A. B. [Journal of the Chemical Society. Perkin transactions I, 1993, # 17, p. 2027 - 2046]

5
[ 5661-55-2 ]
[ 4549-32-0 ]
[ 110425-57-5 ]

Reference： [1]Tetrahedron Letters,1986,vol. 27,p. 5151 - 5154
[2]Journal of the Chemical Society. Perkin transactions I,1993,p. 2027 - 2046

6
[ 5661-55-2 ]
[ 22306-36-1 ]
[ 154218-88-9 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1983,p. 959 - 960

7
[ 5661-55-2 ]
[ 22306-36-1 ]
[ 154218-88-9 ]
1,3-bis(2-oxo-4-phenylazetidin-1-yl)propane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 18% 2: 75%	With potassium hydroxide; tetra(n-butyl)ammonium hydrogensulfate In tetrahydrofuran for 5h; Ambient temperature;

8
[ 5661-55-2 ]
[ 107-80-2 ]
[ 89044-71-3 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1993,p. 2027 - 2046
[2]Journal of the Chemical Society. Chemical communications,1983,p. 959 - 960

9
[ 5661-55-2 ]
[ 3344-70-5 ]
[ 110425-59-7 ]

Reference： [1]Tetrahedron Letters,1986,vol. 27,p. 5151 - 5154
[2]Journal of the Chemical Society. Perkin transactions I,1993,p. 2027 - 2046

10
[ 5661-55-2 ]
[ 89044-65-5 ]
[ 89044-73-5 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1983,p. 959 - 960

11
[ 5661-55-2 ]
[ 76404-99-4 ]
[ 76404-98-3 ]

Reference： [1]Tetrahedron Letters,1983,vol. 24,p. 3669 - 3672
[2]Journal of the American Chemical Society,1981,vol. 103,p. 461 - 462
[3]Heterocycles,1984,vol. 21,p. 279 - 288
[4]Tetrahedron,2002,vol. 58,p. 7177 - 7190

12
[ 52341-70-5 ]
[ 5661-55-2 ]

Yield	Reaction Conditions	Operation in experiment
700 mg	With sodium hydrogencarbonate; sodium hydrogensulfite; In water; at 20℃; for 0.25h;	Freshly distilled styrene (1.04 g, 1.14 mL, 10.0mmol) was dissolved in anhyd toluene (1.0 mL), and the stirred solution was cooled to 15 C. CSI (1.41 g, 0.870 mL, 11.0 mmol) was added dropwise. After 15 min at 15 C, the mixture was slowly added to ice-cold 2% aq NaHCO3. The organic layer was separated and the aqueous layer was extracted with Et2O (3 × 25 mL). The organic layers were combined, dried (Na2SO4), and concentrated under vacuum to give the crude product as a clear oil (IR: 1817 cm-1). The crude product was dissolved in Et2O (2 mL) and the soln was added dropwise to avigorously stirred solution of NaHSO3 (40 mg) and NaHCO3 (360 mg) in H2O (2 mL). The mixture was stirred for 15 min at r.t., the organiclayer was separated, and the aqueous layer was extracted with Et2O(3 × 25 mL). The organic layers were combined and dried (Na2SO4),and then the Et2O was evaporated until the solution became cloudy.

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1993,p. 2027 - 2046
[2]Synthesis,2015,vol. 47,p. 1944 - 1950

13
[ 3646-50-2 ]
[ 5661-55-2 ]

Yield	Reaction Conditions	Operation in experiment
50%	With 2-chloro-1-methyl-pyridinium iodide; triethylamine; In acetonitrile; at 80℃; for 18h;	Step 1: Preparation of 4-phenylazetidin-2-one To a solution of 3-amino-3-phenyl-propanoic acid (2.00 g, 12.1 mmol) in acetonitrile (20 mL) was added 2-chloro-1-methyl-pyridin-1-ium iodide (3.40 g, 13.3 mmol) and triethylamine (2.70 g, 26.6 mmol). The reaction mixture was heated to 80 C. and stirred for 18 h. The mixture was cooled to 25 C. and filtered. The filtrate was concentrated in vacuo. The crude product was purified by column chromatography (silica, petroleum ether/ethyl acetate=10/1 to 1/2) to give 4-phenylazetidin-2-one (0.900 g, 6.12 mmol, 50%) as a white solid. 1H NMR (400 MHz, Chloroform-d) delta 7.47-7.33 (m, 5H), 6.12 (br. s, 1H), 4.76 (dd, J=2.6, 5.3 Hz, 1H), 3.48 (ddd, J=2.4, 5.3, 14.8 Hz, 1H), 2.92 (dd, J=1.6, 14.9 Hz, 1H)
40%	With 2-chloro-1-methyl-pyridinium iodide; triethylamine; In acetonitrile;Reflux; Inert atmosphere;	Compound 1 was prepared using the method of Huang and coworkers (Huang, H.; Iwasawa, N.; Mukaiyama, T. (1984) ?A Convenient Method for the Construction of beta-Lactam Compounds from 13-Amino Acids Using 2-Chloro-1-Methyl Pyridinium Iodide as Condensing Reagent,? Chem. Lett. 1465-1466). In a 1 L round-bottomed flask was combined DL-3-amino-3-phenyl propionic acid (0.007 mol, 1.156 g), 2-chloro-1-methylpyridinium iodide (1.1 eq., 0.0077 mol, 1.74 g), acetonitrile (700 mL) and triethylamine (2.2 eq., 0.0154 mol, 2.15 mL). The reaction was stirred under nitrogen and heated to reflux overnight. The solvent was removed by rotary evaporation and the crude product was purified by column chromatography in 1:1 hexanes:ethyl acetate. Yield: 0.808 g, 40%. 1H NMR (CDCl3) delta 2.84-2.9, m, 1H, 3.40-3.48, m, 1H, 4.71-4.74, m, 1H, 6.38, br s, 1H, 7.2-7.4, m, 5H.

Reference： [1]Journal of the American Chemical Society,1981,vol. 103,p. 2406 - 2408
[2]Chemistry Letters,1984,p. 1465 - 1466
[3]Tetrahedron Letters,1988,vol. 29,p. 2203 - 2206
[4]Synthetic Communications,1988,vol. 18,p. 247 - 252
[5]Chemical and pharmaceutical bulletin,1988,vol. 36,p. 1249 - 1251
[6]Synthetic Communications,2004,vol. 34,p. 1855 - 1862
[7]Tetrahedron Letters,1995,vol. 36,p. 3703 - 3706
[8]Patent: US2019/330198,2019,A1 .Location in patent: Paragraph 1220
[9]Journal of the American Chemical Society,2009,vol. 131,p. 1589 - 1597
[10]Patent: US9120892,2015,B2 .Location in patent: Page/Page column 15; 16
[11]Journal of the Chemical Society. Chemical communications,1988,p. 1242 - 1243
[12]Bulletin of the Chemical Society of Japan,2006,vol. 79,p. 1748 - 1752
[13]Bulletin of the Chemical Society of Japan,2006,vol. 79,p. 1748 - 1752
[14]Monatshefte fur Chemie,2003,vol. 134,p. 343 - 354

14
[ 130533-03-8 ]
[ 5661-55-2 ]

Reference： [1]Journal of Chemical Research, Miniprint,1990,p. 2018 - 2031

15
[ 5661-55-2 ]
[ 98-88-4 ]
[ 731-79-3 ]

Yield	Reaction Conditions	Operation in experiment
75%	With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	Compound 2 was prepared using the method of Park and coworkers (Park, H.; Hepperle, M.; Boge, T. C.; Himes, R. H.; Georg, G. I. (1996) ?Preparation of Phenolic Paclitaxel Metabolites,? J. Med. Chem. 39:2705-2709). In a 25 mL round-bottomed flask was combined (1) (0.0017 mol, 0.250 g), triethylamine (4.63 eq., 0.0073 mol, 1.02 mL), dry methylene chloride (6.3 mL), and dimethylamino pyridine (10 mol %, 1.7 E-4 mol, 0.021 g). The reaction was cooled to 0 C. and benzoyl chloride (3.33 eq., 0.0057 mol, 0.66 mL) was added. The reaction was warmed to room temperature and stirred for 1 h. The reaction was quenched with saturated ammonium chloride (30 mL) and diluted with methylene chloride (150 mL). The reaction mixture was then washed with NaHCO3 and then with brine. The organic portion was dried over MgSO4 and the solvent removed by rotary evaporation. The crude product was purified by column chromatography in 1:1 hexanes:ethyl acetate. Yield: 0.320 g, 75%. 1H NMR (CDCl3) delta 3.094, dd J=16.5, 3.9 Hz, 1H, 3.528, dd J=16.5, 6.9 Hz, 1H, 5.29, m, 1H, 7.26-7.60, m, 8H, 8.01-8.04, m, 2H. 13C {1H}NMR (CDCl3) delta 44.23, 51.56, 125.77, 127.99, 128.26, 128.73, 129.75, 131.68, 133.22, 137.99, 163.91, 165.65. FTIR (ATR): 1675 cm-1, 1735 cm-1, 1778 cm-1, 1795 cm-1. MS-ESI: m/z=525.2 [2M+Na]+.

Reference： [1]Archiv der Pharmazie,1986,vol. 319,p. 635 - 641
[2]Journal of the American Chemical Society,2009,vol. 131,p. 1589 - 1597
[3]Patent: US9120892,2015,B2 .Location in patent: Page/Page column 16

16
[ 5661-55-2 ]
[ 18162-48-6 ]
[ 96746-23-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With triethylamine; In hexane; N,N-dimethyl-formamide;	A. 4-Phenyl-1-(tert.-butyldimethylsilyl)azetidin-2-one 4-Phenylazetidin-2-one (10.4 gm, 71.0 mmole) (Graf, Chem. Ber, 111 (1963); Durst et al. J. Org. Chem., 35, 2043 (1970)) was dissolved in DMF (200 ml) and was treated with tert.-butyldimethylsilyl chloride (12.8 gm, 85 mmol) and triethylamine (11.8 ml, 85 mmol). The mixture was stirred at room temperature for 16 hrs. and taken up in either (500 ml). The ethereal solution was washed with 1N hydrochloric acid (1100 ml), water (250 ml) and brine (1*50 ml). After the solution was dried (anhyd. magnesium sulfate) and evaporated, the residue was flash chromatographed on SiO2 -gel column. Elution with 15% ethyl acetate in hexane afforded 4-phenyl-1-(tert.-butyldimethylsilyl)azetidin-2-one (18.4 gm, 99%) as an oil which solidified on standing. 1 H NMR (CDCl3) delta 7.37-7.29 (5H, m), 4.51 (1H, dd, J=6, 3 Hz), 3.5 (1H, dd, J=16, 6 Hz), 2.93 (1H, dd, J=16, 3 Hz), 0.9 (3H, s), 0.89 (9H, s), 0.19 (3H, s).
99%	With triethylamine; In hexane; N,N-dimethyl-formamide;	A. 4-Phenyl-1-[tert.-butyldimethylsilyl)azetidin-2-one 4-Phenylazetidin-2-one (10.4 gm, 71.0 mmole) (Graf, Chem. Ber, 111 (1963); Durst et al. J. Org. Chem. , 35, 2043 (1970)) was dissolved in DMF (200 ml) and was treated with tert.-butyldimethylsilyl chloride (12.8 gm, 85 mmol) and triethylamine (11.8 ml, 85 mmol). The mixture was stirred at room temperature for 16 hrs. and taken up in ether (500 ml). The ethereal solution was washed with 1 N hydrochloric acid (1 x 100 ml), water (2 x 50 ml) and brine (1 x 50 ml). After the solution was dried (anhyd. magnesium sulfate) and evaporated, the residue was flash chromatographed on SiO2-gel column. Elution with 15% ethyl acetate in hexane afforded 4-phenyl-1-(tert.-butyldimethylsilyl)azetidin-2-one (18.4 gm, 99%) as an oil which solidified on standing. 1H NMR (CDCl3) delta 7.37-7.29 (5H, m), 4.51(1H, dd, J = 6, 3 Hz), 3.5 (1H, dd, J = 16, 6 Hz), 2.93 (1H, dd, J = 16, 3 Hz), 0.9 (3H, s), 0.89 (9H, s), 0.19 (3H, s).

Reference： [1]Patent: US5232929,1993,A
[2]Patent: EP436334,1991,A2
[3]Archiv der Pharmazie,1986,vol. 319,p. 203 - 216

17
[ 5661-55-2 ]
[ 4101-68-2 ]
[ 110425-58-6 ]

Reference： [1]Tetrahedron Letters,1986,vol. 27,p. 5151 - 5154
[2]Journal of the Chemical Society. Perkin transactions I,1993,p. 2027 - 2046

18
[ 87143-23-5 ]
[ 5661-55-2 ]

Reference： [1]Journal of Organic Chemistry,1985,vol. 50,p. 169 - 175
[2]Journal of the Chemical Society. Chemical communications,1983,p. 299 - 301

19
[ 5661-55-2 ]
[ 109-70-6 ]
[ 88909-09-5 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1993,p. 2027 - 2046
[2]Journal of the Chemical Society. Chemical communications,1983,p. 959 - 960
[3]Tetrahedron Letters,1986,vol. 27,p. 5147 - 5150
[4]Journal of the Chemical Society. Perkin transactions I,1993,p. 2055 - 2068

20
[ 5661-55-2 ]
[ 58479-61-1 ]
[ 103247-79-6 ]

Reference： [1]European Journal of Organic Chemistry,2015,vol. 2015,p. 1500 - 1506
[2]Archiv der Pharmazie,1986,vol. 319,p. 203 - 216

21
[ 5661-55-2 ]
[ 76-05-1 ]
[ 21735-63-7 ]

Yield	Reaction Conditions	Operation in experiment
10%	In acetonitrile for 21h; Heating;

Reference： [1]Mattingly; Miller [Journal of Organic Chemistry, 1981, vol. 46, # 8, p. 1557 - 1564]

22
[ 5661-55-2 ]
[ 74-88-4 ]
[ 4458-62-2 ]

Yield	Reaction Conditions	Operation in experiment
0.507 g	With tetrabutylammomium bromide; potassium hydroxide; In tetrahydrofuran; at 25℃; for 8h;	N-Chlorosulfonyl isocyanate (0.846 g, 6 mmol,1.2 equiv) was added dropwise over 10 min to a solution ofstyrene (7) (0.520 g, 5 mmol, 1.0 equiv) in anhydrousdiethyl ether (5 ml) at room temperature under an inertatmosphere. The mixture was stirred at room temperaturefor 2 h, and the solvent was removed under reducedpressure. The residue was taken up in diethyl ether (10 ml)and added dropwise over 10 min to a vigorously stirredsolution of sodium carbonate (1.70 g, 16 mmol, 3.3 equiv)and sodium sulfite (0.882 g, 7 mmol, 1.4 equiv) in water(10 ml) containing ice (10 g). The solution was stirred for 1 hand filtered. The organic layer was separated, while theaqueous layer was extracted with diethyl ether (3×10 ml).The combined organic extracts were dried over anhydrousNa2SO4, filtered, and the solvent was evaporated underreduced pressure to yield <strong>[5661-55-2]4-phenylazetidin-2-one</strong> (8) (0.662 g,4.5 mmol) in a very good yield (90%). The obtainedproduct was dissolved in anhydrous THF (20 ml), thentetrabutylammonium bromide (0.128 g, 0.4 mmol, 0.1 equiv),KOH (0.246 g, 4.4 mmol, 1.0 equiv), and MeI (0.852 g,6.0 mmol, 1.4 equiv) were added and the solution wasstirred for 8 h at 25C. The reaction mixture was filtered,the filtrate was poured into water and extracted with Et2O.The combined organic layers were dried over anhydrousNa2SO4 and evaporated under reduced pressure to yield0.507 g (70%) of 1-methyl-<strong>[5661-55-2]4-phenylazetidin-2-one</strong> (5j) aswhite solid. 1H NMR spectrum (400 MHz, CDCl3), delta, ppm(J, Hz): 2.73 (3H, t, J = 0.9); 2.79 (1H, ddd, J = 14.0, J = 2.3,J = 0.9); 3.35 (1H, ddd, J = 14.0, J = 5.1, J = 0.9); 4.46(1H, dd, J = 5.1, J = 2.3); 7.25-7.41 (5H, m). Intermediate5j was employed without further purification in thereduction reaction. LiAlH4 (0.319 g, 8.4 mmol, 3 equiv) wascarefully added to a solution of AlCl3 (1.11 g, 8.4 mmol,3 equiv) in dry diethyl ether (15 ml) at 0C. The reaction mixture was stirred for 10 min at 0C, then refluxed for 30 min.1-Methyl-<strong>[5661-55-2]4-phenylazetidin-2-one</strong> (5j) (0.451 g, 2.8 mmol,1 equiv) in dry diethyl ether (10 ml) was added slowly and,after the addition was complete, reflux was maintained for4 h. The reaction was cooled to room temperature and 5% aqueous NaOH solution (10 ml) was added carefully. Theaqueous phase was extracted with Et2O (3×10 ml), dried overanhydrous Na2SO4, and evaporated under reduced pressure.

Reference： [1]Archiv der Pharmazie,1986,vol. 319,p. 203 - 216
[2]Chemical Communications,2014,vol. 50,p. 1698 - 1700
[3]Chemistry - A European Journal,2014,vol. 20,p. 12190 - 12200
[4]Chemistry of Heterocyclic Compounds,2017,vol. 53,p. 329 - 334
Khim. Geterotsikl. Soedin.,2017,vol. 53,p. 329 - 334,6

23
4-Phenyl-1-[2-(toluene-4-sulfonyl)-ethyl]-azetidin-2-one [ No CAS ]
[ 5661-55-2 ]

Reference： [1]Journal of Organic Chemistry,1994,vol. 59,p. 5856 - 5857

24
[ 5661-55-2 ]
[ 71864-46-5 ]
[ 185313-27-3 ]

Reference： [1]Pharmazie,1996,vol. 51,p. 811 - 815

25
(+/-)-(trans)-3-bromo-4-phenyl-azetidin-2-one [ No CAS ]
[ 5661-55-2 ]

Reference： [1]Organic Letters,2000,vol. 2,p. 1077 - 1079

26
[ 5661-55-2 ]
[ 105-36-2 ]
[ 67077-19-4 ]

Reference： [1]Archiv der Pharmazie,2000,vol. 333,p. 243 - 253
[2]Monatshefte fur Chemie,2007,vol. 138,p. 627 - 634

27
[ 5661-55-2 ]
[ 3959-05-5 ]
2-phenyl-2,3,5,6-tetrahydro-1H-benzo[b][1,5]diazocin-4-one [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 3529 - 3533

28
[ 5661-55-2 ]
[ 539-74-2 ]
[ 86449-84-5 ]

Reference： [1]Monatshefte fur Chemie,2007,vol. 138,p. 627 - 634

29
[ 5661-55-2 ]
[ 37088-65-6 ]
[ 614-19-7 ]
[ 614-19-7 ]
[ 37088-64-5 ]

Reference： [1]Tetrahedron Asymmetry,2007,vol. 18,p. 1567 - 1573

30
[ 5661-55-2 ]
[ 56613-60-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 84 percent / KOH; Bu₄NBr / tetrahydrofuran 2: 17 percent Turnov_. / H₂

Reference： [1]Achilles, Karin; Schirmeister, Tanja; Otto, Hans-Hartwig [Archiv der Pharmazie, 2000, vol. 333, # 8, p. 243 - 253]

31
[ 5661-55-2 ]
[ 89044-79-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 48 percent / KOH, Bu₄NHSO₄ / tetrahydrofuran / 20 °C 2: 70 percent / liq. NH₃ / 336 h / 45 °C / sealed tube
	Multi-step reaction with 2 steps 1: 41 percent / tetrabutylammonium hydrogen sulfate, KOH / tetrahydrofuran / 8 h / Ambient temperature 2: 74 percent / NH₃ liquid / 336 h / 40 °C

Reference： [1]Crombie, Leslie; Jones, Raymond C. F.; Osborne, Steven; Mat-Zin, Ab. Rasid [Journal of the Chemical Society. Chemical communications, 1983, # 17, p. 959 - 960]
[2]Begley, Michael J.; Crombie, Leslie; Haigh, David; Jones, Raymond C. F.; Osborne, Steven; Webster, Richard A. B. [Journal of the Chemical Society. Perkin transactions I, 1993, # 17, p. 2027 - 2046]

32
[ 5661-55-2 ]
[ 22610-18-0 ]

Yield	Reaction Conditions	Operation in experiment
55%	With lithium aluminium tetrahydride; In diethyl ether; for 4h;Heating / reflux;	Add lithium aluminum hydride (685 mg, 18.1 mmol) to anhydrous ether (20 mL), followed by 4-phenyl-2-azetidinone (760 mg, 5.2 mmol). Heat the mixture to reflux for 4 hr, cool to RT. Add 20% aqueous ammonium chloride solution to quench the reaction, filter through Celite, concentrate and purify (silica gel chromatography, eluding with 10:90 2 M ammonia in methanol:DCM) to give the title compound as a colorless oil (380 mg, 55%). 1H NMR (400 MHz, CDCl3) delta 7.42-7.22 (m, 5H), 4.97 (t, J=8.3 Hz, 1H), 3.82-3.76 (m, 1H), 3.44-3.39 (m, 1H), 2.60-2.38 (m, 3H).
		Preparation 81; 2-Phenyl-azetidine; Dissolve 4-phenyl-azetidin-2-one (1.0 g, 4.28 mmol) in anhydrous THF (20 mL) and treat with 1.0 M solution of lithium aluminum hydride (8.57 mL, 2.0 equiv. ) at room temperature. Stir for 15 h, cool to 0 C in an ice bath and quench with 8.5 mL 1.0 M NaOH then 8.5 mL H2O. Filter resulting solution through celite with additional EtOAc, dry with MgS04, filter and evaporate to yield a milky white oil that solidifies upon standing. Use 2-Phenyl-azetidine without further purification.
		To 0.5 g (3.4 mmol) 4-phenyl-2-azetidinone in 5 ml. anhydrous THF under nitrogen was added a solution of lithium aluminium hydride (1 M in THF, 11.9 mmol) dropwise, and the mixture was heated at reflux for 4 hours. The reaction mixture was cooled to room temperature, 20% aqueous ammonium chloride was added and the mixture was filtered through a pad of celite. The filtrate was extracted with EtOAc (2 x 10 ml_), the organic layers were combined and dried over Na2SC>4. After filtration and evaporation of the solvent the product was purified by column chromatography (silica, DCM/7 N ammonia in MeOH 92:2 to 94:6), which was used in the next step without further purification.

Reference： [1]Patent: US2008/214520,2008,A1 .Location in patent: Page/Page column 18
[2]Patent: WO2005/66126,2005,A1 .Location in patent: Page/Page column 72-73
[3]Patent: WO2010/60952,2010,A1 .Location in patent: Page/Page column 106-107
[4]Chemical Communications,2014,vol. 50,p. 1698 - 1700
[5]Chemical Communications,2015,vol. 51,p. 15588 - 15591

33
[ 292638-84-7 ]
[ 1189-71-5 ]
[ 7757-83-7 ]
[ 5661-55-2 ]

Yield	Reaction Conditions	Operation in experiment
38%	With potassium hydroxide; In diethyl ether; water;	EXAMPLE 9 Preparation of 4-phenylazetidin-2-one (Compound Nr. 20.1) 40 g of styrene are slowly dripped into a solution of 54 g of chlorosulphonylisocyanate in 80 cm3 of ethyl ether, maintaining the solvent at reflux temperature. After three hours the reaction mixture is cooled and is added in small quantities to a solution of 48 g of sodium sulphite in 195 cm3 of water, maintaining the temperature at less than 22 C. with an external ice bath and the pH within a range of between 7 and 8 by adding an aqueous solution of potassium hydroxide at 10%. At the end of the addition the mixture is filtered and the organic phase of the filtrate is dried on sodium sulphate and evaporated. 21 g of the desired compound are obtained (yield 38%).
38%	With potassium hydroxide; In diethyl ether; water;	EXAMPLE 9 Preparation of 4-phenylazetidin-2-one (Compound Nr. 20.1) 40 g of styrene are slowly dripped into a solution of 54 g of chlorosulphonylisocyanate in 80 cm3of ethyl ether, maintaining the solvent at reflux temperature. After three hours the reaction mixture is cooled and is added in small quantities to a solution of 48 g of sodium sulphite in 195 cm3of water, maintaining the temperature at less than 22C with an external ice bath and the pH within a range of between 7 and 8 by adding an aqueous solution of potassium hydroxide at 10%. At the end of the addition the mixture is filtered and the organic phase of the filtrate is dried on sodium sulphate and evaporated. 21 g of the desired compound are obtained (yield 38%).

Reference： [1]Patent: US5856311,1999,A
[2]Patent: EP718280,1996,A2

34
[ 5661-55-2 ]
[ 144-55-8 ]
[ 149193-92-0 ]

Yield	Reaction Conditions	Operation in experiment
47%	With chloro-trimethyl-silane; In ethyl acetate; tert-butyl alcohol;	EXAMPLE 12 Preparation of the tert.-butylic ester of 3-amino-3-phenylpropionic acid (Compound Nr. 12.14). A solution of 10 g of <strong>[5661-55-2]4-phenylazetidin-2-one</strong> and 15.2 g of chlorotrimethylsilane in 150 cm3 of anhydrous tert.-butanol are refluxed for 7 days. The solution is then evaporated and ethyl acetate and aqueous sodium bicarbonate at 5% are added. The organic phase is washed with water, dried on sodium sulphate and is then evaporated. 7 g of tert.- butyl 3-phenyl-3-amino-propanoate are obtained (yield 47%).
47%	With chloro-trimethyl-silane; In ethyl acetate; tert-butyl alcohol;	EXAMPLE 12 Preparation of the tert.-butylic ester of 3-amino-3-phenylpropionic acid (Compound Nr. 12.14). A solution of 10 g of <strong>[5661-55-2]4-phenylazetidin-2-one</strong> and 15.2 g of chlorotrimethylsilane in 150 cm3of anhydrous tert.-butanol are refluxed for 7 days. The solution is then evaporated and ethyl acetate and aqueous sodium bicarbonate at 5% are added. The organic phase is washed with water, dried on sodium sulphate and is then evaporated. 7 g of tert.- butyl 3-phenyl-3-aminopropanoate are obtained (yield 47%).

Reference： [1]Patent: US5856311,1999,A
[2]Patent: EP718280,1996,A2

35
[ 5661-55-2 ]
C₈H₁₁Br [ No CAS ]
C₁₇H₁₉NO [ No CAS ]

Reference： [1]Organic Letters,2008,vol. 10,p. 5187 - 5190

36
[ 5661-55-2 ]
[ 1131726-36-7 ]

Reference： [1]Monatshefte fur Chemie,2008,vol. 139,p. 835 - 846

37
[ 5661-55-2 ]
[ 705-29-3 ]
[ 1131727-48-4 ]

Reference： [1]Monatshefte fur Chemie,2008,vol. 139,p. 835 - 846

38
[ 5661-55-2 ]
[ 1352447-97-2 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 126 - 129

39
[ 5661-55-2 ]
[ 100-39-0 ]
[ 19340-71-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With potassium tert-butylate; In tetrahydrofuran; at 0 - 20℃; for 1h;	To a stirred solution of the appropriate azetidinone2 (10 mmol) and the benzyl bromide (30 mmol) in THF (100 mL) at 0 C was added KOt-Bu (12 mmol) and the reaction stirred at room temperature for 1 h. 2 M aq HCl (20 mL) and water (50 mL) were added and the THF removed by rotary evaporation. The product was extracted into DCM (3 50 mL), dried (MgSO4) and concentrated.Purification by column chromatography on SiO2, initially eluting with 1:1 petroleum ether/DCM to remove the excess benzyl bromide, then DCM to 1% MeOH/DCM to give the product. 4.2.1 N-Benzyl-4-phenyl-azetidin-2-one (1a) Colourless oil (93% yield); spectroscopically consistent with the literature data. 9 Rf (Et2O) 0.5; 1H NMR (500 MHz) delta=2.87 (1H, dd, J=2.2, 14.7 Hz), 3.34 (1H, dd, J=5.1, 14.7 Hz), 3.76 (1H, d, J=15.0 Hz), 4.40 (1H, dd, J=2.2, 5.1 Hz), 4.80 (1H, d, J=15.0 Hz), 7.14 (2H, d, J=7.2 Hz), 7.20-7.40 (8H, m); 13C NMR+DEPT (125 MHz) delta=44.8 (CH2), 47.0 (CH2), 53.6 (CH), 126.6 (CH), 127.8 (CH), 128.6 (CH), 128.8 (CH), 129.1 (CH), 135.6 (C), 138.0 (C), 167.3 (C).