[ CAS No. 36476-87-6 ]

Name: 36476-87-6|1-(Diphenylmethyl)azetidine-3-carboxylic Acid|98%
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Quality Control of [ 36476-87-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 36476-87-6 ]

Product Details of [ 36476-87-6 ]

CAS No. :	36476-87-6	MDL No. :	MFCD01566539
Formula :	C₁₇H₁₇NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BRSCYENHLCPOAU-UHFFFAOYSA-N
M.W :	267.32 g/mol	Pubchem ID :	2735440
Synonyms :

Calculated chemistry of [ 36476-87-6 ]

Physicochemical Properties

Num. heavy atoms :	20
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.24
Num. rotatable bonds :	4
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	81.59
TPSA :	40.54 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.59 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.27
Log Po/w (XLOGP3) :	0.48
Log Po/w (WLOGP) :	2.09
Log Po/w (MLOGP) :	2.62
Log Po/w (SILICOS-IT) :	2.67
Consensus Log Po/w :	2.03

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.98
Solubility :	2.8 mg/ml ; 0.0105 mol/l
Class :	Very soluble
Log S (Ali) :	-0.9
Solubility :	33.6 mg/ml ; 0.126 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-4.27
Solubility :	0.0143 mg/ml ; 0.0000533 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	1.64

Safety of [ 36476-87-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P301+P312-P302+P352-P304+P340-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 36476-87-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 36476-87-6 ]
Downstream synthetic route of [ 36476-87-6 ]

[ 36476-87-6 ] Synthesis Path-Upstream 1~2

1
[ 36476-87-6 ]
[ 74-88-4 ]
[ 53871-06-0 ]

Yield	Reaction Conditions	Operation in experiment
80.8%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 20.5 h;	Potassium carbonate (6.53 g) and iodomethane (0.976 ml) were added to a solution of 1-benzhydrylazetidine-3-carboxylic acid (4.20 g) in N,N-dimethylformamide (45 ml), followed by stirring at room temperature for 20.5 hours. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=5:1, then 3:1). The fractions containing the target compound were concentrated to give the title compound (3.57 g, 80.8percent) as yellow crystals.¹H-NMR Spectrum (CDCl₃) δ (ppm): 3.26 (2H, m), 3.31 (1H, m), 3.44 (2H, m), 3.69 (3H, s), 4.38 (1H, s), 7.16-7.20 (2H, m), 7.25-7.28 (4H, m), 7.39-7.41 (4H, m).ESI-MS (m/z): 282[M+H]⁺.
80.8%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 20.5 h;	(Production Example 84) Methyl 1-benzhydrylazetidine-3-carboxylate A solution of 1-benzhydrylazetidine-3-carboxylic acid (4.20 g) in N,N-dimethylformamide (45 ml) were added potassium carbonate (6.53 g) and iodomethane (0.976 ml), followed by stirring at room temperature for 20.5 hr. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate = 5:1, then 3:1). Fractions containing the target compound were concentrated to provide the titled compound as yellow crystals (3.57 g, 80.8 percent). ¹H-NMR Spectrum (CDCl₃) δ (ppm): 3.26 (2H, m), 3.31 (1H, m), 3.44 (2H, m), 3.69 (3H, s), 4.38 (1H, s), 7.16-7.20 (2H, m), 7.25-7.28 (4H, m), 7.39-7.41 (4H, m). ESI-MS (m/z): 282 [M+H]⁺.

Reference： [1] Patent: US2008/214815, 2008, A1, . Location in patent: Page/Page column 14
[2] Patent: EP1889836, 2008, A1, . Location in patent: Page/Page column 80

2
[ 67-56-1 ]
[ 36476-87-6 ]
[ 53871-06-0 ]

Reference： [1] Patent: US2010/249399, 2010, A1, . Location in patent: Page/Page column 21

[ 36476-87-6 ] Synthesis Path-Downstream 1~29

3
[ 36476-87-6 ]
[ 74-88-4 ]
[ 53871-06-0 ]

Yield	Reaction Conditions	Operation in experiment
80.8%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 20.5h;	Potassium carbonate (6.53 g) and iodomethane (0.976 ml) were added to a solution of 1-benzhydrylazetidine-3-carboxylic acid (4.20 g) in N,N-dimethylformamide (45 ml), followed by stirring at room temperature for 20.5 hours. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=5:1, then 3:1). The fractions containing the target compound were concentrated to give the title compound (3.57 g, 80.8percent) as yellow crystals.1H-NMR Spectrum (CDCl3) delta (ppm): 3.26 (2H, m), 3.31 (1H, m), 3.44 (2H, m), 3.69 (3H, s), 4.38 (1H, s), 7.16-7.20 (2H, m), 7.25-7.28 (4H, m), 7.39-7.41 (4H, m).ESI-MS (m/z): 282[M+H]+.
80.8%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 20.5h;	(Production Example 84) Methyl 1-benzhydrylazetidine-3-carboxylate A solution of 1-benzhydrylazetidine-3-carboxylic acid (4.20 g) in N,N-dimethylformamide (45 ml) were added potassium carbonate (6.53 g) and iodomethane (0.976 ml), followed by stirring at room temperature for 20.5 hr. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate = 5:1, then 3:1). Fractions containing the target compound were concentrated to provide the titled compound as yellow crystals (3.57 g, 80.8 percent). 1H-NMR Spectrum (CDCl3) delta (ppm): 3.26 (2H, m), 3.31 (1H, m), 3.44 (2H, m), 3.69 (3H, s), 4.38 (1H, s), 7.16-7.20 (2H, m), 7.25-7.28 (4H, m), 7.39-7.41 (4H, m). ESI-MS (m/z): 282 [M+H]+.

Reference： [1]Patent: US2008/214815,2008,A1 .Location in patent: Page/Page column 14
[2]Patent: EP1889836,2008,A1 .Location in patent: Page/Page column 80

4
[ 36476-87-6 ]
azetidine hydrochloride [ No CAS ]
[ 928038-41-9 ]

Yield	Reaction Conditions	Operation in experiment
65%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	1-Benzhydrylazetidine-3-carboxylic acid (1.52 g) was dissolved in N,N-dimethylformamide (30 ml) at room temperature under a nitrogen atmosphere. Triethylamine (3.17 ml), BOP reagent (benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate; 5.03 g) and azetidine hydrochloride (1.06 g) were added in this order, followed by stirring for 24 hours. A 1N aqueous solution of sodium hydroxide (50 ml) was added to the reaction mixture, followed by stirring. Then the reaction mixture was extracted after addition of ethyl acetate (100 ml). The separated organic layer was washed with a 1N aqueous solution of sodium hydroxide, water and brine, and dried over anhydrous sodium sulfate. To the residue (1.83 g) obtained by distilling off the solvent were added ethyl acetate (2 ml) and tert-butyl methyl ether (10 ml) to precipitate crystals. The crystals were collected by filtration, and dried under aeration to give the title compound (1.14 g, 65%) as pale yellow crystals.1H-NMR Spectrum (CDCl3) δ (ppm): 2.15-2.30 (2H, m), 3.20-3.50 (5H, m), 3.90-4.10 (4H, m), 4.45 (1H, s), 7.15-7.45 (10H, m).ESI-MS (m/z): 307[M+H]+.
65%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	(Production Example 99) 3-(Azetidin-1-ylcarbonyl)-1-benzhydrylazetidine 1-Benzhydrylazetidine-3-carboxylic acid (1.52 g) was dissolved in N,N-dimethylformamide (30 ml) at room temperature under a nitrogen atmosphere. Triethylamine (3.17 ml), BOP reagent (5.03 g), and azetidine hydrochloride (1.06 g) were added in this order, followed by stirring for 24 hr. To the reaction mixture was added a 1N aqueous solution of sodium hydroxide (50 ml), followed by stirring. The liquid-liquid separation was carried out after addition of ethyl acetate (100 ml). The separated organic layer was washed with a 1N aqueous solution of sodium hydroxide, water and brine in this order, and dried over anhydrous sodium sulfate. To the residue (1.83 g) obtained by removing the solvent were added ethyl acetate (2 ml) and tert-butyl methyl ether (10 ml) to precipitate crystals. The crystals were collected by filtration and dried under aeration to provide the titled compound as pale yellow crystals (1.14 g, 65 %). 1H-NMR Spectrum (CDCl3) δ (ppm): 2.15-2.30 (2H, m), 3.20-3.50 (5H, m), 3.90-4.10 (4H, m), 4.45 (1H, s), 7.15-7.45 (10H, m). ESI-MS (m/z): 307 [M+H]+.

Reference： [1]Patent: US2008/214815,2008,A1 .Location in patent: Page/Page column 16-17
[2]Patent: EP1889836,2008,A1 .Location in patent: Page/Page column 83

5
[ 36476-87-6 ]
[ 1068-57-1 ]
[ 1009368-02-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	Compound 34A. N'-acetyl-l-benzhydrylazetidine-S-carbohydrazidev y Ph HN-NH v Phλ[00217] To a solution of l-benzhydrylazetidine-3-carboxylic acid (2.097 g, 7.845 mmol) and acetohydrazine (0.967 g, 11.767 mmol) in DMF (40 mL) was added HOBt (1.59 g, 11.767 mmol) and EDAC (2.255 g, 11.767 mmol), followed by /-Pr2NEt (2.1 mL, 11.767 mmol). The mixture was stirred at room temperature overnight. Solvent was removed and the residue was purified via Prep HPLC to provide compound 34A as white solid (2.4 g, 95% yield). LC/MS (m/z) = 324 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 7.48 (d, J=7.1 Hz, 4 H), 7.28 - 7.42 (m, 6 H), 5.40 (s, 1 H), 4.30 (br. s., 2 H), 3.84 - 4.10 (m, 3 H), 1.84 - 2.07 (m, rotomer, 3 H).
	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;	To 1 -benzhydrylazetidine-3-carboxyl ic acid (prepared according to patent US2008/2 14815Al, page 73 exampe 83) in DCM (10 mL) was added acetohydrazide (commerciallyavailable) and triethylamine (2.321 mL, 16.65 mmol) followed by T3P 50% in DMF (2.92 mL, 5.00 mmol) dropwise and the mixture was stirred at room temperature for 2 h. T3P (50% in DMF) (2.92 mL, 5.00 mmol), was added and the mixture was stirred for a further 1 h. The resulting mixture was partitioned between EtOAc and water and the aqueous layer wasremoved. The organic layer was washed with saturated sodium bicarbonate solution, water, brine and dried using a phase separating column. The solvent was removed under reduced pressure. Purification of the crude product by chromatography on silica using a gradient from 0 - 100% EtOAc in iso-hexane followed by methanol in EtOAc (10%) afforded the title compound as a yellow oil that solidified. The crude product was used in the next step withoutfurther purification.

Reference： [1]Patent: WO2008/24892,2008,A2 .Location in patent: Page/Page column 116
[2]Patent: WO2015/8230,2015,A1 .Location in patent: Page/Page column 331

6
[ 6638-79-5 ]
[ 36476-87-6 ]
[ 359402-66-7 ]

Yield	Reaction Conditions	Operation in experiment
55%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 1h;	1- [3- (Dimethylamino) propyl]-3-ethylcarbodiimide hydrochloride (8.0 g, 42 mmol) was added to a suspension of1-benzhydryl-azetidine-3-carboxylic acid (7.42 g, 27.8 mmol), NO-dimethyl-hydroxyl-amine hydrochloride (4.24g, 43.5 mmol), and triethylamine (11.6mil, 83.3 mmol) in dichloromethane (150 mL). The suspension was then stirred at room temperature for 60 minutes. The suspension was diluted with dichloromethane (300 mL), and the resulting solution was washed with water (3 x 100 mL). The organic layer was then dried (magnesium sulfate), filtered, and concentrated under reduced pressure. The resulting solid was purified via medium pressure liquid chromatography eluting with dichloromethane: methanol (40: 1) to deliver 4.76 g (55 % yield) of the title compound as a white solid (mp103-106 C) ; MS (APCI+):m/z 311(M+H) +.
55%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 1h;	1- [3- (Dimethylamino) propyl]-3-ethylcarbodiimide hydrochloride (8. 0 g, 42 mmol) was added to a suspension of1-benzhydryl-azetidine-3-carboxylic acid (7.42 g, 27.8 mmol), NO-dimethyl-hydroxyl-amine hydrochloride (4.24g, 43.5 mmol), and triethylamine (11.6 mL, 83.3 mmol) in dichloromethane (150 mL). The suspension was then stirred at room temperature for 60 minutes. The suspension was diluted with dichloromethane (300 mL), and the resulting solution was washed with water (3 x 100 mL). The organic layer was then dried (magnesium sulfate), filtered, and concentrated under reduced pressure. The resulting solid was purified via medium pressure liquid chromatography eluting with dichloromethane: methanol (40: 1) to deliver 4.76 g (55 % yield) of the title compound as a white solid (mp103-106 C) ; MS (APCI+): m/z 311 (M+H)+.

Reference： [1]Patent: WO2005/49602,2005,A1 .Location in patent: Page/Page column 83; 84; 112
[2]Patent: WO2005/49605,2005,A1 .Location in patent: Page/Page column 111; 112; 140

7
[ 36476-87-6 ]
[ 72351-36-1 ]

Yield	Reaction Conditions	Operation in experiment
54%		1-Benzhydryl-3-azetidinecarboxylic acid (3.12 g) was suspended in tetrahydrofuran (60 ml), and cooled in an ice-methanol bath under a nitrogen atmosphere. Triethylamine (1.96 ml) was added dropwise, and a solution of ethyl chlorocarbonate (1.34 ml) in tetrahydrofuran (5 ml) was added dropwise over 20 minutes. After the addition, the reaction mixture was stirred at the same temperature for 30 minutes. The reaction mixture was filtered, and the residue was washed with tetrahydrofuran (30 ml). The filtrate was added dropwise to a solution of an aqueous (15 ml) solution of sodium borohydride (1.33 g) cooled in an ice water bath over 15 minutes. After the addition, the reaction mixture was stirred at room temperature. 1N hydrochloric acid (35 ml) was gradually added to the reaction mixture to degrade excess sodium borohydride, and a 1N aqueous solution of sodium hydroxide (35 ml) was added. This was extracted with ethyl acetate (100 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated, and the residue was dried under reduced pressure to give the title compound (1.59 g, 54%) as a pale brown solid.1H-NMR Spectrum (CDCl3) δ (ppm): 2.57 (1H, m), 3.03 (2H, m), 3.24 (2H, m), 3.80 (2H, d, J=5.2 Hz), 4.33 (1H, s), 7.15-7.45 (10H, m).ESI-MS (m/z): 254[M+H]+.
54%		(Reference Example F-4) 1-Benzhydryl-3-(hydroxymethyl)azetidine 1-Benzhydryl-3-azetidinecarboxylic acid (3.12 g) was suspended in tetrahydrofuran (60 ml) and cooled under a nitrogen atmosphere in an ice-ethanol bath. Triethylamine (1.96 ml) was added dropwise, and a solution of ethyl chlorocarbonate (1.34 ml) in tetrahydrofuran (5 ml) was added dropwise over 20 min. After the dropwise addition, stirring was carried out at the same temperature for 30 min. The reaction mixture was filtered and washed with tetrahydrofuran (30 ml). The filtrate was added dropwise over 15 min to an aqueous (15 ml) solution of sodium borohydride (1.33 g) cooled in an ice water bath. Upon completion of the dropwise addition, the reaction mixture was stirred at room temperature. To the reaction mixture was gradually added 1N hydrochloric acid (35 ml) to decompose excess sodium borohydride, and a 1N aqueous solution of sodium hydroxide (35 ml) was added. This was extracted with ethyl acetate (100 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated, and the residue was dried under reduced pressure to provide the titled compound as a pale brown solid (1.59 g, 54 %). 1H-NMR Spectrum (CDCl3) δ (ppm): 2.57 (1H, m), 3.03 (2H, m), 3.24 (2H, m), 3.80 (2H, d, J = 5.2 Hz), 4.33 (1H, s), 7.15-7.45 (10H, m). ESI-MS (m/z):254[M+H]+.
54%		(Production Example 102) 1-Benzhydryl-3-(hydroxymethyl)azetidine 1-Benzhydryl-3-azetidinecarboxylic acid (3.12 g) was suspended in tetrahydrofuran (60 ml) and cooled under a nitrogen atmosphere in an ice-ethanol bath. Triethylamine (1.96 ml) was added dropwise, and a solution of ethyl chlorocarbonate (1.34 ml) in tetrahydrofuran (5 ml) was added dropwise over 20 min. After the dropwise addition, stirring was carried out at the same temperature for 30 min. The reaction mixture was filtered and washed with tetrahydrofuran (30 ml). The filtrate was added dropwise over 15 min to an aqueous (15 ml) solution of sodium borohydride (1.33 g) cooled in an ice water bath. Upon completion of the dropwise addition, the reaction mixture was stirred at room temperature. To the reaction mixture was gradually added 1N hydrochloric acid (35 ml) to decompose excess sodium borohydride, and a 1N aqueous solution of sodium hydroxide (35 ml) was added. This was extracted with ethyl acetate (100 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated, and the residue was dried under reduced pressure to provide the titled compound as a pale brown solid (1.59 g, 54 %). 1H-NMR Spectrum (CDCl3) δ (ppm): 2.57 (1H, m), 3.03 (2H, m), 3.24 (2H, m), 3.80 (2H, d, J = 5.2 Hz), 4.33 (1H, s), 7.15-7.45 (10H, m). ESI-MS (m/z):254[M+H]+.

		65.1. (1 -Benzhydryl-azetidin-3-yl)-methanol: l-Benzhydrylazetane-3-carboxylic acid (101 mg) was dissolved in THF (2 mL) and lithium aluminium hydride (27 mg) was added. The mixture was stirred overnight at RT. Water, sodium potassium tartrate solution and EA were added. The phases were separated, the org. phase was dried (Na2SO4) and evaporated off to afford 93 mg of the desired product. LC-MS (A): tR = 0.67 min; [M+H]+: 254.16.
	With lithium aluminium tetrahydride; In tetrahydrofuran;Heating / reflux;	A solution of 1-(diphenylmethyl)-3-(hydroxymethyl) azetidine (1 g, 3.9 mmol) [prepared by reduction of 1-(diphenylmethyl)azetidine-3-carboxylic acid (CAS No.: 36476-87-6) using LiAlH4 in refluxing THF] and Et3N (0.71 mL, 5.1 mmol) in THF (30 mL) was treated with methanesulfonyl chloride (0.36 mL, 4.7 mmol) and stirred for 2 h at room temperature. The precipitate was removed by filtration and washed with THF. The liquors were evaporated and the residue partitioned between water and DCM. The DCM layer was separated and the aqueous re-extracted. The combined organics were washed with brine, dried (Na2SO4), filtered and evaporated. The residue was triturated with isohexane, the solid then isolated by filtration and dried to give the title compound as an orange solid (1.1g, 84%). m/z (ES+) 332 (M+H)+.

Reference： [1]Patent: WO2006/72353,2006,A1 .Location in patent: Page/Page column 53
[2]Patent: US2008/214815,2008,A1 .Location in patent: Page/Page column 17
[3]Patent: EP2119706,2009,A1 .Location in patent: Page/Page column 48
[4]Patent: EP1889836,2008,A1 .Location in patent: Page/Page column 83
[5]Patent: WO2009/69100,2009,A1 .Location in patent: Page/Page column 116
[6]Patent: US2005/101586,2005,A1 .Location in patent: Page/Page column 6

8
[ 36476-86-5 ]
[ 36476-87-6 ]

Yield	Reaction Conditions	Operation in experiment
71.7%		Potassium hydroxide (6.48 g) and water (3.25 ml) were added to a solution of 1-benzhydryl-3-cyanoazetidine (5.43 g) in methoxyethanol (54 ml), followed by stirring at 100 C. for 4 hours. The reaction mixture was allowed to cool down to room temperature, and poured into ice. After pH of the mixture was adjusted to 5 with 1N hydrochloric acid, sodium chloride was added thereto. This was extracted with a mixed solvent of ethyl acetate and tetrahydrofuran. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The dried organic layer was concentrated under reduced pressure to give a crude product of the title compound as pale yellow crystals. The crystals were suspended by the addition of diethyl ether (15 ml). The crystals were collected by filtration and washed with diethyl ether. This was dried under aeration to give the title compound (4.20 g, 71.7%) as pale yellow crystals.1H-NMR Spectrum (CDCl3) δ (ppm): 3.00-3.90 (5H, m), 4.95 (1H, s), 7.25-7.28 (2H, m), 7.33 (4H, m), 7.53 (4H, m).
71.7%		(Reference Example F-3) 1-Benzhydrylazetidine-3-carboxylic acid To a solution of 1-benzhydryl-3-cyanoazetidine (5.43 g) in methoxyethanol (54 ml) were added potassium hydroxide (6.48 g) and water (3.25 ml), followed by stirring at 100 C for 4 hr. The reaction mixture was allowed to cool down to room temperature. The reaction mixture was poured into ice. After adjusting this to pH 5 with 1N hydrochloric acid, sodium chloride was added thereto. This was extracted with a mixed solvent of ethyl acetate and tetrahydrofuran. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer after drying was concentrated under reduced pressure to provide a crude product of the titled compound as pale yellow crystals. The crystals were suspended by addition of diethyl ether (15 ml). The crystals were collected by filtration and washed with diethyl ether. This was dried under aeration to provide the titled compound as pale yellow crystals (4.20 g, 71.7 %). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.00-3.90 (5H, m), 4.95 (1H, s), 7.25-7.28 (2H, m), 7.33 (4H, m), 7.53 (4H, m).
71%		A suspension of 1-benzhydryl-azetidine-3-carbonitrile (2.09 g, 8. 42 mmol) in concentrated hydrochloric acid (12 M, 15 mL) was heated at reflux for 30 minutes. The resulting solution was cooled to0 C, and 6 M sodium hydroxide was added until the mixture reached a pH of about 7. The aqueous mixture was <Desc/Clms Page number 112>then extracted with dichloromethane (3 x 150 mL) and dichloromethane: methanol (10: 1,3 x 150 mL). The combined organic layers were dried, filtered, and concentrated under reduced pressure to give the title compound (1.60 g, 71 % yield). MS (APCI): m/z 268(M+H)'.

71%		A suspension ofl-benzhydryl-azetidine-3-carbonitrile (2.09 g, 8.42 mmol) in concentrated hydrochloric acid (12 M, 15 mL) was heated at reflux for 30 minutes. The resulting solution was cooled to0 C, and 6 M sodium hydroxide was added until the mixture reached a pH of about 7. The aqueous mixture was <Desc/Clms Page number 140>then extracted with dichloromethane (3 x 150 mL) and dichloromethane: methanol (10: 1,3 x 150 mL). The combined organic layers were dried, filtered, and concentrated under reduced pressure to give the title compound (1.60 g, 71 % yield). MS (APCI): m/z 268(M+I+.
71.7%		(Production Example 83) 1-Benzhydrylazetidine-3-carboxylic acid To a solution of 1-benzhydryl-3-cyanoazetidine (5.43 g) in methoxyethanol (54 ml) were added potassium hydroxide (6.48 g) and water (3.25 ml), followed by stirring at 100 C for 4 hr. The reaction mixture was allowed to cool down to room temperature. The reaction mixture was poured into ice. After adjusting this to pH 5 with 1N hydrochloric acid, sodium chloride was added thereto. This was extracted with a mixed solvent of ethyl acetate and tetrahydrofuran. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer after drying was concentrated under reduced pressure to provide a crude product of the titled compound as pale yellow crystals. The crystals were suspended by addition of diethyl ether (15 ml). The crystals were collected by filtration and washed with diethyl ether. This was dried under aeration to provide the titled compound as pale yellow crystals (4.20 g, 71.7 %). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.00-3.90 (5H, m), 4.95 (1H, s), 7.25-7.28 (2H, m), 7.33 (4H, m), 7.53 (4H, m).
	With potassium hydroxide; In 2-ethoxy-ethanol; water; ethyl acetate;	(1-Benzhydrylazetidin-3-yl)carboxylic acid may be prepared by carrying out the procedure in the following manner: a solution of 11 g of potassium hydroxide in 9 cm3 of water is added dropwise to a suspension, cooled to +5 C., of 14 g of (1-benzhydrylazetidin-3-yl)carbonitrile in 140 cm3 of 2-ethoxyethanol and then the mixture is heated to 95 C. After stirring for 16 hours at this temperature, the reaction mixture is poured slowly, with stirring, over ice and left at 0 C. for 68 hours and then concentrated to dryness to dryness at 50 C. under reduced pressure (2.7 kPa). The residue is taken up in 400 cm3 of water, the solution is acidified to pH 4 with 6 N hydrochloric acid and then supplemented with 400 cm3 of ethyl acetate. The resulting suspension is filtered, the solid is drained and then dried at 50 C. under reduced pressure (2.7 kPa). 13.55 g of (1-benzhydrylazetidin-3-yl)carboxylic acid are obtained in the form of a cream-colored solid.
		(3) A mixture of the above product (5.79 g), sodium hydroxide (2.57 g) and 50% aqueous ethanol (50 ml) was heated to reflux for 6 hours with stirring. After cooled to 0 C., the mixture was adjusted to pH3 with concentrated hydrochloric acid, and extracted with chloroform. The extract was sequentially washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give 1-diphenylmethylazetidine-3-carboxylic acid (about 6.5 g) as a yellow amorphous solid. The solid was used in the next step without any purification.
	In water;Acidic conditions;	A solution of diphenylmethanamine (benzhydrylamine) and 2-oxopropane- 1,3 -diyl dimethanesulfonate were reacted to give 1 -benzhydrylazetidin-3-one 10 (Scheme 2). Reduction of the ketone of 10 with a hydride reducing agent gave 1-benzhydrylazetidin-3-ol11. Alternatively, 11 can be prepared by cyclization of benzhydrylamine and epichlorohydrin in diisopropylethylamine and ethanol. Mesylation of with methanesulfonyl chloride gave 1 -benzhydrylazetidin-3 -yl methanesulfonate 12. Displacement of the mesyl group with cyanide ion gave 1 -benzhydrylazetidine-3-carbonitrile 13. Hydrolysis of 13 with aqueous acid gave 1 -benzhydrylazetidine-3-carboxylic acid 14. Deprotection of 14 by hydrogenolysisgave 1 (CAS Reg. No.: 36476-78-5 zwitterion; 102624-46-4 hydrochloride salt; 106887-11-0 sodium salt; 1282041 potassium salt).

Reference： [1]Patent: US2008/214815,2008,A1 .Location in patent: Page/Page column 14
[2]Patent: EP2119706,2009,A1 .Location in patent: Page/Page column 48
[3]Patent: WO2005/49602,2005,A1 .Location in patent: Page/Page column 82; 84; 111; 112
[4]Patent: WO2005/49605,2005,A1 .Location in patent: Page/Page column 111; 112; 139; 140
[5]Patent: EP1889836,2008,A1 .Location in patent: Page/Page column 79
[6]Patent: US2001/27193,2001,A1
[7]Patent: US2010/249399,2010,A1 .Location in patent: Page/Page column 21
[8]Patent: WO2018/108954,2018,A1 .Location in patent: Page/Page column 19

9
[ 667940-67-2 ]
[ 36476-87-6 ]
C₄₄H₅₀N₄O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With N-ethyl-N,N-diisopropylamine; HATU; In DMF (N,N-dimethyl-formamide); at 0℃;	The starting material D was prepared according to the following scheme; D To a solution of A (3 g; 6.67 mmol) in DMF (10 ml) were successively added at 0C diisopropylethylamine (1.74 ml; 10 mmol, 1.5 equiv. ), B (2.14 g; 8 mmol, 1.2 equiv. ) and HATU (3.04g ; 8 mmol, 1.2 equiv. ). The mixture was stirred over a week end. After removal of DMF under reduced pressure, a saturated aqueous solution of NaHC03 was added and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over MgS04. The solvent was evaporated and the residue purified by flash chromatography eluting with 80/20 ethyl acetate/petroleum ether to give C (4.1 g). Yield: 88%

Reference： [1]Patent: WO2005/80402,2005,A1 .Location in patent: Page/Page column 57

10
[ 36476-87-6 ]
1-Diphenylmethyl-3-(N-[2-hydroxyethyl]-N-methylcarbamoyl)azetidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Preparations 62 to 64 The compounds of the following tabulated Preparations of the general formula: STR428 were prepared by a similar procedure to that of Preparation 59 using <strong>[36476-87-6]1-diphenylmethylazetidine-3-carboxylic acid</strong> and the appropriate amine as starting materials.

Reference： [1]Patent: US5968923,1999,A

11
[ 53871-06-0 ]
[ 36476-87-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In tetrahydrofuran; methanol;	PREPARATION 12-1) To a solution of <strong>[53871-06-0]1-(diphenylmethyl)-3-methoxycarbonylazetidine</strong> (28 g) in methanol (270 ml) and tetrahydrofuran (130 ml) was added 1N sodium hydroxide (115 ml) and the solution was stirred at room temperature for 1.5 hours. The solution was then concentrated to remove organic solvents under reduced pressure. The resultant aqueous solution was adjusted to pH 2.95 with 10percent hydrochloric acid, and resulting precipitates were collected by filtration, washed with water and dried to give 1-(diphenylmethyl)-3-carboxyazetidine (24.7 g). mp: 138°-140° C. NMR (DMSO-d6, delta): 3.09-3.45 (5H, m), 4.42 (1H, s), 7.13-7.43 (10H, m).

Reference： [1]Patent: US5102877,1992,A

12
[ 557-66-4 ]
[ 36476-87-6 ]
[ 530-62-1 ]
[ 91189-21-8 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In chloroform; acetonitrile;	1-(Diphenylmethyl)-N-ethyl-3-azetidinecarboxamide To a solution of 7.5 g (28 mmole) of 1-(diphenylmethyl)azetidine-3-carboxylic acid in 75 ml of acetonitrile was added 6.0 g (37 mmole) of 1,1'-carbonyldiimidazole. The reaction was heated at 60 C. for two hours and successively treated with 3.1 g (30.8 mmole) of triethylamine and 2.52 g (30.8 mmole) of ethylamine hydrochloride. The reaction was stirred at 60 C. for an additional hour, the solvent evaporated in vacuo and the residue dissolved in chloroform. After washing with water and drying over magnesium sulfate, the chloroform layer was evaporated in vacuo to give 9.4 g of 1-(diphenylmethyl)-N-ethyl-3-azetidinecarboxamide, mp 91-93 C.

Reference： [1]Patent: US4638067,1987,A

13
[ 36476-87-6 ]
[ 530-62-1 ]
[ 91196-84-8 ]

Yield	Reaction Conditions	Operation in experiment
	With methylamine hydrochloride; triethylamine; In chloroform; acetonitrile;	EXAMPLE Z 1-(Diphenylmethyl)-N-methyl-3-azetidinecarboxamide To a solution of 7.5 g (28 mmole) of 1-(diphenylmethyl)azetidine-3-carboxylic acid in 75 ml of acetonitrile was added 6.0 g (37 mmole) of 1,1'-carbonyldiimidazole. The reaction was heated at 60 C. for two hours and successively treated with 3.11 g (30.8 mmole) of triethylamine and 2.08 g (30.8 mmole) of methylamine hydrochloride. The reaction was stirred at 60 C. for an additional hour, the solvent evaporated in vacuo, and the residue dissolved in chloroform. After washing with water and drying over magnesium sulfate, the chloroform layer was evaporated in vacuo to give 9.0 g of 1-(diphenylmethyl)-N-methyl-3-azetidinecarboxamide, mp 103-107 C.
	With methylamine hydrochloride; triethylamine; In chloroform; acetonitrile;	EXAMPLE Z 1-(Diphenylmethyl)-N-methyl-3-azetidinecarboxamide To a solution of 7.5 g (28 mmole) of 1-(diphenylmethyl)azetidine-3-carboxylic acid in 75 ml of acetonitrile was added 6.0 g (37 mmole) of 1,1'-carbonyldiimidazole. The reaction was heated at 60 C. for two hours and successively treated with 3.11 g (30.8 mmole) of triethylamine and 2.08 g (30.8 mmole) of methylamine hydrochloride. The reaction was stirred at 60 C. for an additional hour, the solvent evaporated in vacuo, and the residue dissolved in chloroform. After washing with water and drying over magnesium sulfate, the chloroform layer was evaporated in vacuo to give 9.0 g of 1-(diphenylmethyl)-N-methyl-3-azetidinecarboxamide, mp 103-107 C.

Reference： [1]Patent: US4638067,1987,A
[2]Patent: US4771054,1988,A

14
[ 36476-87-6 ]
[ 1025712-89-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With thionyl chloride; at 20℃; for 4h;	Step 1: l-Benzhydrylazetidine-3-carbonyl chloride hydrochloride; [00269] l-Benzhydrylazetidine-3-carboxylic acid (16.0 g, 59.8 mmol) was added portionwise to thionyl chloride (50 mL), and the resulting mixture was stirred at room temperature for 4 h. Thionyl chloride was then removed under reduced pressure. The residue was triturated with THF (50 ml) which was then evaporated. l-Benzhydrylazetidine-3-carbonyl chloride hydrochloride (19.3 g, 100 %) was isolated as a beige solid, and used without further purification.

Reference： [1]Patent: WO2008/55959,2008,A1 .Location in patent: Page/Page column 64

15
[ 36476-87-6 ]
[ 124-40-3 ]
[ 927390-59-8 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 6h;	Step 1: 1-Benzhydryl-N,N-dimethyl-3-azetidinecarboxamide; 1-Benzhydryl-3-azetidinecarboxylic acid (1.17 g), dimethylamine (2 mole solution in tetrahydrofuran, 2.6 ml), triethylamine (0.67 ml) and 1-hydroxybenzotriazole (300 mg) were dissolved in dichloromethane (25 ml) and cooled on ice. Then, the solution was added with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (925 mg), and the mixture was returned to room temperature, and stirred for 6 hours. The reaction mixture was added with saturated aqueous sodium hydrogencarbonate, and extracted with ethyl acetate. The organic layer was successively washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel chromatography [developing solvent; ethyl acetate:n-hexane=2:1 (v/v)] to obtain the title compound (1.10 g) as colorless solid. 1H-NMR (400MHz, CDCl3) δ : 2.85 (3H, s), 2.92 (3H, s), 3.23-3.29 (2H, m), 3.46-3.48 (3H, m), 4.38 (1H, s), 7.16-7.41 (10H, m).

Reference： [1]Patent: EP1942109,2008,A1 .Location in patent: Page/Page column 13-14

16
[ 67-56-1 ]
[ 36476-87-6 ]
[ 53871-06-0 ]

Yield	Reaction Conditions	Operation in experiment
		(4) To a solution of the above product (about 6.5 g) in methanol (60 ml) was added concentrated sulfuric acid (6 ml), and the mixture was heated to reflux for 1 hour with stirring. After cooled to room temperature, the solvent was removed in vacuo, and the residue was dissolved in chloroform. The solution was washed with water, 5percent sodium bicarbonate aqueous solution, water and brine in that order, and then dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give 1-diphenylmethylazetidine-3-carboxylic acid methyl ester (4.9 g) as a brown powder. 1H-NMR (CDCl3, deltappm); 3.2-3.4, 3.4-3.5 (5H, m), 3.69 (3H, s), 4.39 (1H, s), 7.2-7.3, 7.3-7.45 (10H, m). LC-MS, m/z; 282 (MH+).

Reference： [1]Patent: US2010/249399,2010,A1 .Location in patent: Page/Page column 21

17
[ 36476-87-6 ]
[ 618-39-3 ]
C₂₄H₂₃N₃O [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2011,vol. 76,p. 1177 - 1179

18
[ 36476-87-6 ]
[ 618-39-3 ]
[ 1263815-93-5 ]

Reference： [1]Journal of Organic Chemistry,2011,vol. 76,p. 1177 - 1179

19
[ 593-51-1 ]
[ 36476-87-6 ]
[ 91196-84-8 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃;	Step 1 1-Benzhydryl-N-methylazetidine-3-carboxamide 400 mg of 1-benzhydrylazetidin-3-carboxylic acid (synthesized according to the method described in WO2005/49602) was dissolved in 4 ml of dimethylformamide, and 683 mg of triethylamine, 122 mg of methylamine hydrochloride, 304 mg of 1-hydroxybenzotriazole and 431 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride were added thereto, and the mixture was stirred at room temperature overnight. The reaction solution was diluted with ethyl acetate. The solution was washed in turn with water and brine and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and then the obtained residue was purified by silica gel column chromatography to obtain 158 mg of the objective compound.
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃;	step 1 1-benzhydryl -N- methyl azetidinecarboxylic-3-carboxamide1-benzhydryl azetidine-3-carboxylic acid400Mg( WO synthesized according to the 2005/49602) the N, was dissolved in N- dimethylformamide 4 ml, triethylamine 683 mg, methylamine hydrochloride 122 mg, 1-hydroxybenzotriazole 304mg and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride 431mg was added, at room temperature It was stirred overnight.The reaction mixture was diluted with ethyl acetate, washed successively with water and saturated brine, and dried with magnesium sulfate.Under reduced pressure, the solvent was distilled off, the resulting residue was purified by silica gel column chromatography to give the title compound 158 mg.

Reference： [1]Patent: US2011/288065,2011,A1 .Location in patent: Page/Page column 53
[2]Patent: JP5668756,2015,B2 .Location in patent: Paragraph 0138

20
[ 36476-87-6 ]
[ 1009368-03-9 ]

Reference： [1]Patent: WO2015/8230,2015,A1

21
diethyl 4-((3aR,5R,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate [ No CAS ]
[ 36476-87-6 ]
(1-benzhydrylazetidin-3-yl)((3aR,6R,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methanone [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 6610 - 6613
Angew. Chem.,2018,vol. 130,p. 6720 - 6723,4

22
[ 36476-87-6 ]
[ 74-89-5 ]
[ 91196-84-8 ]

Yield	Reaction Conditions	Operation in experiment
88.2%	With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; dichloromethane; at 23℃; for 1h;	Step 1: 1-Benzhydryl-N-methylazetidine-3-carboxamide To a solution of <strong>[36476-87-6]1-benzhydrylazetidine-3-carboxylic acid</strong> (4.0 g, 14.96 mmol, 1.0 eq), and CH3NH2 (8.98 mL, 17.96 mmol, 1.2 eq, 2 M in THF) in CH2Cl2 (60 mL) was added EDCI (5.74 g, 29.93 mmol, 2.0 eq), HOBt (3.03 g, 22.44 mmol, 1.5 eq) and DIEA (9.89 mmol, 59.85 mmol, 4.0 eq) sequently. The resulting mixture was stirred at 23 C. for 1 hour. The mixture was diluted with water (60 mL), then the organic phase was washed with brine (3*60 mL), dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography eluting with DCM/methanol to give the title compound (3.70 g, 88.2% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.36-7.34 (m, 4H), 7.24-7.22 (m, 4H), 7.18-7.14 (m, 2H), 6.06 (s, 1H), 4.39 (s, 1H), 3.32 (t, J=8.0 Hz, 2H), 3.25 (t, J=6.0 Hz, 2H), 3.06-2.98 (m, 1H), 2.82 (d, J=4.8 Hz, 3H).

Reference： [1]Patent: US2018/271837,2018,A1 .Location in patent: Paragraph 0149-0150

23
[ 18621-17-5 ]
[ 36476-87-6 ]

Reference： [1]Patent: EP1889836,2008,A1

24
[ 33301-41-6 ]
[ 36476-87-6 ]

Reference： [1]Patent: EP1889836,2008,A1

25
[ 36476-87-6 ]
[ 928038-42-0 ]

Reference： [1]Patent: EP1889836,2008,A1

26
[ 36476-87-6 ]
[ 1025712-92-8 ]

Reference： [1]Patent: WO2008/55959,2008,A1

27
[ 36476-87-6 ]
C₂₆H₃₁N₅O₂ [ No CAS ]

Reference： [1]Patent: WO2008/55959,2008,A1

28
C₂₂H₂₅NO₄ [ No CAS ]
[ 36476-87-6 ]

Yield	Reaction Conditions	Operation in experiment
78 g	With hydrogenchloride; at 80℃;	Add 120g of the intermediate product (C) prepared in Example 2 to 1L of 6N hydrochloric acid, heat to 80C, keep the temperature for overnight, and generate gas. Take care to prevent flushing. The next day, evaporate the water to obtain a brown oily substance. , 300 mL of acetone was added for heating and recrystallization to obtain 78 g of intermediate product (D), which was pale yellow solid in appearance.

Reference： [1]Patent: CN108069889,2021,B .Location in patent: Paragraph 0027-0028

29
[ 36476-87-6 ]
[ 36476-78-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With 10% palladium hydroxide on charcoal; hydrogen; In methanol; water; under 22502.3 Torr; for 6h;	78 g of the intermediate product (D) prepared in Example 3 was added to a mixture of 500 mL of methanol and 100 mL of water, 7 g of palladium hydroxide on carbon (10%) was added, and hydrogen gas was introduced into it to make the pressure of the reaction vessel reach 3 MPa After 6 hours of reaction, the reaction was complete, the catalyst was removed by filtration, 500 mL of water was added, the methanol was distilled off, the diphenylmethane was extracted twice with ethyl acetate, the water layer was concentrated to dryness, and the obtained solid was added to 300 mL of water again, and the pH was adjusted with potassium carbonate solid. 6.7 There is turbidity. Extract with ethyl acetate, dry the organic layer, and concentrate to dryness to obtain 25 g of azetidine-3-carboxylic acid as a solid product, with a yield of 85%.

Reference： [1]Patent: CN108069889,2021,B .Location in patent: Paragraph 0029-0030

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P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 36476-87-6 ]

Quality Control of [ 36476-87-6 ]

Related Doc. of [ 36476-87-6 ]

Product Details of [ 36476-87-6 ]

Calculated chemistry of [ 36476-87-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 36476-87-6 ]

Application In Synthesis of [ 36476-87-6 ]

[ 36476-87-6 ] Synthesis Path-Upstream 1~2

[ 36476-87-6 ] Synthesis Path-Downstream 1~29

Related Functional Groups of [ 36476-87-6 ]

Aryls

Carboxylic Acids

Related Parent Nucleus of [ 36476-87-6 ]

Azetidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 36476-87-6 ]

Related Parent Nucleus of
[ 36476-87-6 ]