Name: 82-07-5|Xanthene-9-carboxylic acid|98%
Brand: Ambeed
SKU: A840780
Price: 7.0 USD
Availability: InStock
Rating: 97 (25 reviews)

1
[ 82-07-5 ]
[ 5490-92-6 ]

Reference： [1]RSC Advances,2017,vol. 7,p. 46615 - 46620
[2]Angewandte Chemie - International Edition,2015,vol. 54,p. 10596 - 10599
Angew. Chem.,2015,vol. 127,p. 10742 - 10745,4
[3]Canadian Journal of Chemistry,1957,vol. 35,p. 1084,1085
[4]Tetrahedron Letters,1986,vol. 27,p. 823 - 826
[5]Journal of Medicinal Chemistry,1998,vol. 41,p. 346 - 357
[6]Tetrahedron Letters,2001,vol. 42,p. 6645 - 6647
[7]Annali di Chimica,1959,vol. 49,p. 1321,1327

2
[ 82-07-5 ]
[ 26454-53-5 ]

Yield	Reaction Conditions	Operation in experiment
	With oxalyl dichloride;N,N-dimethyl-formamide; In chloroform; at 0 - 20℃; for 1h;	2 g of 9H-Xanthene-9-carboxylic acid (0.0088 mol) were dissolved in 30 ml of CHCI3 (ethanol free). The solution was cooled at 0C and 1.08 ml (0.0123 mol) of oxalyl chloride and a drop of DMF was added. The mixture was stirred and allowed to warm to room temperature. After an hour at this temperature the solvents were evaporated and the residue was dissolved in CHCI3 and evaporated again. This procedure was repeated two times. The solid obtained (2.19 g) was dissolved in 20 ml of CHCI3 and added to a solution of 0.975 g (0.0097 mol) of (3R)-1-methylpyrrolidin-3-ol (Intermediate 1-19) in 15 ml of CHCI3 cooled at 0-5C. The reaction mixture was allowed-to warm to room temperature and stirred overnight. The solvent was evaporated and the residue was dissolved in toluene and extracted with HCI 2N. The aqueous layer was basified with K2CO3 and extracted with CHCI3. The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness to yield 2.53 g (93%) of the title product as an oil. 1H-NMR (CDCl3): No. 1. 65-1.85 (m, 1 H), 2.05-2. 42 (m, 2H), 2.30 (s, 3H), 2.45-2. 60 (m, 1H), 2.60-2. 80 (m, 2H), 5.0 (s, 1 H), 5.05-5. 20 (m, 1 H), 7.0-7. 25 (m, 4H), 7.25-7. 40 (m, 4H). MS [M+1] + : 310

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 5076 - 5092
[2]Journal of the American Chemical Society,1992,vol. 114,p. 230 - 241
[3]Synthesis,1982,vol. No. 12,p. 1023 - 1025
[4]Journal of Medicinal Chemistry,1994,vol. 37,p. 268 - 274
[5]Patent: WO2003/87094,2003,A2 .Location in patent: Page/Page column 28

3
[ 82-07-5 ]
[ 79673-91-9 ]

Reference： [1]Synthesis,1981,p. 616 - 620

4
[ 82-07-5 ]
[ 90-47-1 ]

Reference： [1]Journal of Chemical Research - Part S,1998,p. 820 - 821
[2]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 3394 - 3398
[3]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3433 - 3435
[4]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 903 - 906

5
[ 82-07-5 ]
[ 2862-03-5 ]
[ 150629-67-7 ]
[ 292150-20-0 ]
Fmoc-L-Ala [ No CAS ]
(R)-2-{(S)-2-[(R)-2-((2S,3R,4R,5S,6R)-3-Acetylamino-2-benzyloxy-5-hydroxy-6-hydroxymethyl-tetrahydro-pyran-4-yloxy)-propionylamino]-propionylamino}-pentanedioic acid 1-amide 5-({(S)-1-carbamoyl-5-[(9H-xanthene-9-carbonyl)-amino]-pentyl}-amide) [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 1361 - 1363

6
[ 50541-93-0 ]
[ 82-07-5 ]
N-(1-benzylpiperidin-4-yl)-9H-xanthene-9-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1429 - 1435

7
[ 82-07-5 ]
[ 87120-72-7 ]
[ 202796-60-9 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1429 - 1435
[2]Patent: US9375474,2016,B2 .Location in patent: Sheet 6 of 15

8
[ 82-07-5 ]
4-amino-1-(cyclooctenylmethyl)piperidine [ No CAS ]
N-[1-(cyclooctenylmethyl)piperidin-4-yl]xanthene-9-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1429 - 1435

9
[ 50-34-0 ]
[ 82-07-5 ]

Yield	Reaction Conditions	Operation in experiment
	With water at 100℃; for 1.16667h;

Reference： [1]Hanna; Lau-Cam [Pharmazie, 2001, vol. 56, # 9, p. 700 - 703]

10
[ 82-07-5 ]
[ 5680-83-1 ]
N-(benzyloxycarbonylglycyl)-N'-(xanthen-9-ylcarbonyl)hydrazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate In N,N-dimethyl-formamide at 0 - 20℃; for 2.5h;

Reference： [1]El-Faham; Abdul-Ghani [Organic Preparations and Procedures International, 2003, vol. 35, # 4, p. 369 - 374]

11
[ 6154-04-7 ]
[ 82-07-5 ]
9H-xanthene-9-carboxylic acid (2-methyl-2H-tetrazol-5-yl)-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 4628 - 4631

12
[ 95112-14-4 ]
[ 82-07-5 ]
9H-xanthene-9-carboxylic acid (2-ethyl-2H-tetrazol-5-yl)-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1,1'-carbonyldiimidazole at 0 - 20℃;

Reference： [1]Vieira, Eric; Huwyler, Joerg; Jolidon, Synese; Knoflach, Frederic; Mutel, Vincent; Wichmann, Juergen [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 20, p. 4628 - 4631]

13
[ 82-07-5 ]
[ 497233-85-9 ]
9<i>H</i>-xanthene-9-carboxylic acid (3-{4-[3-(7-chloro-quinolin-4-ylamino)-propyl]-piperazin-1-yl}-propyl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 5300 - 5308

14
[ 82-07-5 ]
[ 3272-96-6 ]
[ 1009621-50-4 ]

Yield	Reaction Conditions	Operation in experiment
78%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 18h;	A mixture of 9H-<strong>[82-07-5]xanthene-9-carboxylic acid</strong> (1.46g, 6.5mmol), 2-chloro-N-hydroxy- acetamidine (1 g, 9.3 mmol), O-(7-azobenzotriazol-1 -yl)-1 ,1 ,3,3-tetramethyluronium hexafluorophosphate (3.0 g, 7.5 mmol) and diisopropylethylamine (3 ml) in DMF (15 ml) was stirred at room temperature for 18 h. The reaction mixture was partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate. The combined organic phases were dried (Na2SO4) and concentrated in vacuo to leave a yellow oil. Purification by flash column chromatography on a silica isolute cartridge eluting with pentane, 4:1 -1 :1 pentane-ether, and ethyl acetate gave the title compound as a pale orange solid, (1.5 g, 78%).

Reference： [1]Patent: WO2008/23157,2008,A1 .Location in patent: Page/Page column 123

15
[ 82-07-5 ]
[ 5813-90-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	With pyridine; di-tert-butyl dicarbonate; ammonium bicarbonate; In 1,4-dioxane; at 20℃; for 12h;	10 g (44.2 mmol) of xanthen-9-carboxylic acid and 11.6 g (53.0 mmol, 1.2 eq) of EPO <DP n="40"/>(Boc)2O were added. Then, 2.1 g (26.5 mmol, 0.6 eq) of pyridine and 5.3 g (66.3 mmol, 1.5 eq) Of NH4HCO3 were added thereto. Then, 100 ml of 1,4-dioxane was added thereto to dissolve them. Thereafter, the solution was stirred for 12 hours at room temperature. After the reaction was completed, the reactant was extracted with an organic layer by using EA/H2O. The organic layer was concentrated, and then diethyl ether was added for crystallization thereto. The resultant solution was stirred for 1 hr and then filtered to obtain 8.47 g (85%) of 9H-xanthen-9-carboxamide.1H NMR (200 MHz, CDCl3) delta 7.8(brs, IH) 7.33~7.24(m, 4H) 7.13~7.05(m, 5H) 4.88(s, IH)

Reference： [1]Patent: WO2007/15632,2007,A1 .Location in patent: Page/Page column 38-39
[2]Annali di Chimica,1959,vol. 49,p. 1321,1327

16
[ 82-07-5 ]
[ 637-59-2 ]
[ 194218-97-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With n-butyllithium; In tetrahydrofuran; hexane; at 0 - 20℃; for 16.4667h;pH 14.0;	To a solution of 10 g (44 mmol, 1 eq) of 9-xanthenylcarboxylic acid in 200 mL of THF at 0C was added 37.2 mL (93 mmol, 2.1 eq) of a 2.5 M solution of n-butyllithium in hexanes dropwise over 15 min. (First equivalent resulted in precipitation of Li salt of the carboxylate; solution became homogeneous as dianion formed.) The resulting orange solution of dianion was stirred at 0C for 10 min and 9.4 mL (62 mmol, 1.4 eq) of 1-bromo-3-phenylpropane was added quickly over 3 min. The reaction was stirred at 0C and allowed to warm to RT as the ice bath melted. After 16 h, the basic reaction mixture (pH -14) was extracted with water (3 x 100 mL). The combined aqueous layers were acidified (to pH ~1) with 6 N HCl and extracted with ether (3 x 100 mL). The combined ether solutions were dried (MgSO4), filtered and concentrated to afford 17.04 g of a viscous golden oil. The oil was dissolved in hot hexanes using a small amount of CH2Cl2 to effect complete dissolution. Concentration of this solution resulted in a yellow solid which was recrystallized from ether/hexanes to afford' 13.3 g (88%) of title compound as a white crystalline solid, m.p. 137-138C. TLC (silica gel, 10% MeOH in CH2Cl2, UV and I2) Rf = 0.52.
13.3 g (88%)	With n-butyllithium; In tetrahydrofuran;	A. 9-(3-Phenylpropyl)-9H-<strong>[82-07-5]xanthene-9-carboxylic acid</strong> To a solution of 10 g (44 mmol, 1 eq) of 9-xanthenylcarboxylic acid in 200 mL of THF at 0 C. was added 37.2 mL (93 mmol, 2.1 eq) of a 2.5M solution of n-butyllithium in hexanes dropwise over 15 min. (First equivalent resulted in precipitation of Li salt of the carboxylate; solution became homogeneous as dianion formed.) The resulting orange solution of dianion was stirred at 0 C. for 10 min and 9.4 mL (62 mmol, 1.4 eq) of 1-bromo-3-phenylpropane was added quickly over 3 min. The reaction was stirred at 0 C. and allowed to warm to RT as the ice bath melted. After 16 h, the basic reaction mixture (pH ~14) was extracted with water (3100 mL). The combined aqueous layers were acidified (to pH ~1) with 6N HCl and extracted with ether (3100 mL). The combined ether solutions were dried (MgSO4), filtered and concentrated to afford 17.04 g of a viscous golden oil. The oil was dissolved in hot hexanes using a small amount of CH2 Cl2 to effect complete dissolution. Concentration of this solution resulted in a yellow solid which was recrystallized from ether/hexanes to afford 13.3 g (88%) of title compound as a white crystalline solid, m.p. 137-138 C.

Reference： [1]Patent: EP904262,2004,B1 .Location in patent: Page 80
[2]Patent: US5760246,1998,A

17
[ 1476-11-5 ]
[ 82-07-5 ]
[ 194219-20-0 ]

Yield	Reaction Conditions	Operation in experiment
66%	With n-butyllithium; In tetrahydrofuran; hexane; at 0℃; for 24h;	To a stirred solution of 5.00 g (22.1 mmol) of xanthene carboxylic acid in 100 mL of THF at 0C was added 19.5 mL (48.7 mmol) of 2.5 M butyllithium in hexanes followed by 3.05 g (24.32 mmol) of cis-1,4-dichloro-2-butene. The reaction was allowed to stir at 0C for 24 h when the mixture was diluted with 250 mL of ethyl acetate and 100 mL or 0.5 M HCl. The layers were separated, the organics dried (Na2SO4) and concentrated. The remainder was purified by flash column chromatography on silica gel (250 g) eluting with 30:70:0.5 ethyl acetate/hexanes/acetic acid to give 4.6 g (66%) of title compound as a white solid. mp 134-135C.

Reference： [1]Patent: EP904262,2004,B1 .Location in patent: Page 140

18
[ 155748-81-5 ]
[ 82-07-5 ]
9H-xanthene-9-carboxylic acid-[(3-benzyl)-3-azabicyclo[3.1.0]-hex-6-yl] amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 4-methyl-morpholine; DMF (N,N-dimethyl-formamide); butan-1-ol; at 0 - 20℃; for 3.5h;	A solution OF XANTHENE-9-CARBOXYLIC acid (Lancaster Synthesis, Windham NH) (0.25g, 1 eqv) AND N-3-BENZYL-3-AZABICYCLO [3.1. 0] hex-6-yl-amine (0.31 g, 1.5 eqv) (procedure of T. F. Braish et. al. , Synlett, 1996,1100) in DIMETHYLFORMAMIDE was cooled to 0C. Butanol was then added followed by the addition of N-methyl morpholine (NMM). The reaction mixture was stirred for 30 minutes at 0C. 1- (3-dimethylaminopropyl)-3- ethyl carbodiimide hydrochloride (EDC) was then added and the reaction mixture was again stirred for 3 hr at 0C. It was then allowed to stir at room temperature and the organic compound 9H-<strong>[82-07-5]xanthene-9-carboxylic acid</strong>- b iz y a z b y o [3. 1. 0]-HEX-6- yl]-amide (0. 35G) was extracted with dichloromethane. The solvent dichloromethane was evaporated under reduced pressure and dried under vacuuo. The organic compound was purified by column chromatography. The melting point was 217-219C ; 1HNM (CDC13) : 7. 39-7. 32 (M, 2H), 7. 30-7. 07 (M, 11H), H 5. 20 (BS, 1H), 4. 85 (S, 2H), 3. 02-2. 93 (M, 3H), 2. 29 (D, 2H, J=6HZ), 1. 28-1. 26 (M, 2H) ; mass (m/z) : 397 ; IR (KBR) : 3296, 2788, 1684 CM-

Reference： [1]Patent: WO2004/56810,2004,A1 .Location in patent: Page 11-12

19
[ 720680-79-5 ]
[ 82-07-5 ]
[ 720680-77-3 ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 4-methyl-morpholine; DMF (N,N-dimethyl-formamide); butan-1-ol; at 0 - 20℃; for 3.5h;	A solution OF XANTHENE-9-CARBOXYLIC x n h n 9 b o x y acid (Lancaster) (0. 25 G, 1 EQV.) and N-3- benzyl-3-azabicyclo [3. 1. 0] hex-6-yl-methyl amine (procedure OF EP E P 0, 413, 455 A2) in DIMETHYLFBRMAMIDE were taken and cooled to 0C. Butanol and N-methyl morpholine (NMM) were also added subsequently. The solution was allowed to stir for 30 minutes at 0C. 1- (3-DIMETHYLAMINOPROPYL)-3-ETHYLCARBODIIMIDE hydrochloride (EDC) was then added and the stirring was continued for 3 hr at 0C. The reaction mixture was then stirred at room temperature. The reaction mixture was diluted with water and then extracted the organic compound 9H-XANTHENE-9-CARBOXYLIC ACID- (3-BENZYL)-3-AZABICYCLO [3.1. 0] -hex-6- yl] amide with ethyl acetate. Evaporated ethyl acetate under reduced pressure and dried under vacuuo. The purification was done by column chromatography using silica gel. Column was eluted with a mixture of ethyl acetate: hexane (10: 90); Ethyl acetate: hexane (20: 80); Ethyl acetate: Hexane (30: 70); Ethyl acetate: Hexane (50: 50); Ethyl Acetate: Hexane (65: 25) to yield 80 mg of the desired product. The melting point was 181-183C ; HNMR (CDC13) 8 : 7.39 (d, 2H, J=7.6 Hz), 7.31-7. 09 (M, 11H), 5.27 (bs, 1H), 4.87 (s, 1H), 3.52 (s, 2H), 3.00-2. 95 (M, 2H), 2.80 (d, 2H, J=8.5 Hz), 2.23 (d, 2H, J=8.6 Hz), 1.25- 1.19 (M, 1H), 1.10 (M, 2H); Mass. (m/z): 411.2.

Reference： [1]Patent: WO2004/56810,2004,A1 .Location in patent: Page 12-13

20
[ 82-07-5 ]
[ 151860-17-2 ]
N-[(1α,5α,6α)-3-benzyl-3-aza-bicyclo[3.1.0]hex-6-ylmethyl]-9H-xanthene-9-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 25h;	Synthesis of N-[Y1 a, 5 a, 6 a)-3-benzyl-3-aza-bicvclor3.1.01hex-6-yll-9H-Xanthene-9-carboxylic acid amide; A solution of 9H- <strong>[82-07-5]xanthene-9-carboxylic acid</strong> (commercially available) (1.0 eq) and (1 a, 5 a, 6 a/)-6-amino-3-benzyl-3-aza-bicyclo[3.1.0]hexane (0.95 eq) in dimethylformamide was cooled to 0C. To the resulting reaction mixture was added hydroxybenzotriazole (1 eq) and N-methylmorpholine (2eq). The reaction mixture was stirred for 30 minutes at 0C followed by the addition of l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (leq). The reaction mixture was again stirred for 1 hour at 0C and thereafter it was stirred at room temperature for 24 hours. The reaction mixture was poured into water under stirring and extracted with ethylacetate. The solvent was evaporated under reduced pressure and the residue thus obtained was purified by column chromatography to furnish the title compound.
		A solution of 9H-<strong>[82-07-5]xanthene-9-carboxylic acid</strong> (commercially available) (1.0 eq) and (1alpha,5alpha,6alpha)-6-amino-3-benzyl-3-aza-bicyclo[3.1.0]hexane (0.95 eq) in dimethylformamide was cooled to 0+ C. To the resulting reaction mixture was added hydroxybenzotriazole (1 eq) and N-methylmorpholine (2 eq). The reaction mixture was stirred for 30 minutes at 0 C. followed by the addition of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1 eq). The reaction mixture was again stirred for 1 hour at 0 C. and thereafter it was stirred at room temperature for 24 hours. The reaction mixture was poured into water under stirring and extracted with ethylacetate. The solvent was evaporated under reduced pressure and the residue thus obtained was purified by column chromatography to furnish the title compound.

Reference： [1]Patent: WO2006/5980,2006,A1 .Location in patent: Page/Page column 11
[2]Patent: US2008/319002,2008,A1 .Location in patent: Page/Page column 6

21
[ 1366664-25-6 ]
[ 82-07-5 ]
9H-xanthene-9-carboxylic acid [(1α,5α,6α)-3-benzyl-3-aza-bicyclo[3.1.0]hex-6-ylmethyl] ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In toluene; for 8h;Heating / reflux;	Example 1: Synthesis of 9H-Xanthene-9-carboxylic acid (l cl 5 <x 6 a)-3-benzyl-3-aza-bicyclo[3.1.0]hex-6-ylmethyr\| ester (Compound No. 1); To a solution of 9H-<strong>[82-07-5]xanthene-9-carboxylic acid</strong> (1.1 eq) and (1 a, 5 a, 6 ce)-3-benzyl-6-methanesulphonyloxymethyl-3-aza-bicyclo[3.1.0]hexane (1.0 eq) in toluene, was added l,8-diazabicyclo[5.4.0]undecane-4-ene (1 eq). The reaction mixture was refluxed for about 8 hours and then cooled to room temperature and stirred for overnight. The reaction mixture was quenched with sodium bicarbonate solution and toluene layer was separated. The organic layer was washed with water, brine and dried over anhydrous sodium sulphate. The organic layer was concentrated under reduced pressure. The residue thus obtained was purified by column chromatography to furnish the title compound (46%).m.p: softening start at 85C.IR(KBr): 1733.7 cm"1lH NMR (CDC13):8 6.94-7.23 (m, 13H), 4.92 (s, 1H), 3.81-3.83 (m, 2H), 3.50 (s, 1H),2.78-2.81 (m, 2H), 1.97-2.01 (m, 2H), 1.14-1.25 (m, 1H), 0.88-0.93 (m, 2H).Mass (m/z): 412 (M++l)
46%		To a solution of 9H-<strong>[82-07-5]xanthene-9-carboxylic acid</strong> (1.1 eq) and (1alpha,5alpha,6alpha)-3-benzyl-6-methanesulphonyloxymethyl-3-aza-bicyclo[3.1.0]hexane (1.0 eq) in toluene, was added 1,8-diazabicyclo[5.4.0]undecane-4-ene (1 eq). The reaction mixture was refluxed for about 8 hours and then cooled to room temperature and stirred for overnight. The reaction mixture was quenched with sodium bicarbonate solution and toluene layer was separated. The organic layer was washed with water, brine and dried over anhydrous sodium sulphate. The organic layer was concentrated under reduced pressure. The residue thus obtained was purified by column chromatography to finish the title compound (46%). m.p: softening start at 85 C. IR (KBr): 1733.7 cm-1 1H NMR (CDCl3):delta 6.94-7.23 (m, 13H), 4.92 (s, 1H), 3.81-3.83 (m, 2H), 3.50 (s, 1H), 2.78-2.81 (m, 2H), 1.97-2.01 (m, 2H), 1.14-1.25 (m, 1H), 0.88-0.93 (m, 2H). Mass (m/z): 412 (M++1)

Reference： [1]Patent: WO2006/5980,2006,A1 .Location in patent: Page/Page column 12
[2]Patent: US2008/319002,2008,A1 .Location in patent: Page/Page column 6

22
[ 82-07-5 ]
[ 188027-95-4 ]

Yield	Reaction Conditions	Operation in experiment
6.98 g (55.2%)	With hydrogenchloride; N-chloro-succinimide; In water; acetic acid;	EXAMPLE 8 2,7-Dichloroxanthene-9-carboxylic Acid: To a suspension of 10 g of <strong>[82-07-5]xanthene-9-carboxylic acid</strong> and 14 g of N-chlorosuccinimide in 80 mL of acetic acid was added with stirring dropwise 2.0 mL of conc. HCl over a period of 5 minutes. The mixture was stirred at room temperature for 12 hours and quenched by the addition of 150 mL of water. The precipitated solid was removed by filtration, rinsed with water, and dried in air to give 12.6 g (100%) of the crude carboxylic acid as a white solid. Recrystallization from MeOH--EtOAc (2:1) gave 6.98 g (55.2%) of the pure 2,7-dichloro<strong>[82-07-5]xanthene-9-carboxylic acid</strong> as colorless small needles, m.p. 273-275 C. (dec.); IR (KBr): 2970 (b, OH), 1695 (C=O) cm-1; 1 H NMR (DMSO-d6): delta 5.01 s, 1H, CH), 7.05-7.50 (m, 6H, aryl). Anal. Calcd for C14 H8 Cl2 O3: C, 56.98; H, 2.73. Found: C, 57.05; H, 2.74.
	With hydrogenchloride; N-chloro-succinimide; acetic acid; In water; at 20℃; for 48h;	Intermediate 422,7-dichloro-9H-<strong>[82-07-5]xanthene-9-carboxylic acid</strong>Acetic acid (80 ml.) and N-chlorosuccinimide (14.7 g, 110 mmols) were added to <strong>[82-07-5]xanthene-9-carboxylic acid</strong> (10.0 g, 44 mmols). Hydrochloric acid (2 ml.) was added dropwise to the mixture at room temperature and it was stirred under these conditions for EPO <DP n="77"/>48 hours. Water was added (150 mL) and the precipitate was filtered. The product obtained was used without further purification in the synthesis of example 54.

Reference： [1]Patent: US5101059,1992,A
[2]Patent: WO2006/133802,2006,A1 .Location in patent: Page/Page column 75-76

23
[ 82-07-5 ]
[ 74-88-4 ]
[ 39497-06-8 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 1h;	To a suspension of 9H-<strong>[82-07-5]xanthene-9-carboxylic acid</strong> (20 g, 88.4 mmol) and Cs2CO3 (34.5 g, 106 mmol) in dimethyl formamide (300 mL), methyl iodide (8.3 mL, 133 mmol) is added dropwise at RT. The reaction is stirred for 1h before it is quenched with water and extracted with diethyl ether. The organic phase is washed twice with water and with brine, dried over Na2SO4, filtered and evaporated to yield the title compound as a yellow solid. TLC, Rf (hexane/ethyl acetate 2/1) = 0.72.

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2196 - 2206
[2]Patent: WO2006/117183,2006,A1 .Location in patent: Page/Page column 74

24
C₁₃H₂₀N₃O₃Pol [ No CAS ]
[ 82-07-5 ]
C₂₇H₂₈N₃O₅Pol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 102; N-(2-((3-endo)-8-(4-chlorobenzyl)-8-azabicvclof3.2.noctan-3-ylamino)-2-oxoethyl)-9H- xanthene-9-carboxamidePS-allyl (3-endo)-3-(glycylamino)-8-azabicyclo[3.2.1]octane-8-carboxylate (Intermediate 19) (0.06 g, loading: 1 mmol/g, 0.06 mmol) was washed and swelled with dichloromethane. A solution of 0.8 mmols of DIEA and 0.4 mmols of <strong>[82-07-5]xanthene-9-carboxylic acid</strong> in dichloromethane/dimethylformamide 9:1 (1mL) was added and it was stirred at room temperature for 10 minutes. Then 0.4 mmols of 0-(7-azabenzotriazol-1-yl)-N,N,N',N'- tetramethyluronium hexafluorophosphate (HATU) was added. The mixture was stirred for 2 hours at room temperature. It was filtered and washed with dichlorometane/dimethylformamide 9:1 (3X), dimethylformamide (3x) and dichloromethane (3X). The resin was dried in vacuo.The subsequent allyloxycarbonyl (alloc) deprotection of PS-allyl (3-endo)-3-[N-(9H- xanthen-9-ylcarbonyl)glycyl]amino}-8-azabicyclo[3.2.1 ]octane-8-carboxylate, the reductive amination with 4-chlorobenzaldehide and the final cleavage were performed following the procedures described above for example 48. Reverse phase chromatography gave the title compound (0.008 g).

Reference： [1]Patent: WO2006/133802,2006,A1 .Location in patent: Page/Page column 155

25
(3R)-N-methylquinuclidin-3-amine [ No CAS ]
[ 82-07-5 ]
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-N-methyl-9H-xanthene-9-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%		Oxalyl chloride (0.540 ml, 0.0062 mol) was added to a solution of 9H-xanthene-9- carboxylic acid (1.16 [G,] 0.0051 mol) and [DIMETHYLFORMAMIDE] (two drops) in 20 ml of [CHC13] (ethanol free) at [0C.] The mixture was allowed to warm to room temperature under stirring and maintained 1 h at this temperature. After this time, the reaction mixture was concentrated to dryness in vacuo and the obtained residue was dissolved in [CHIC13] (15 [ML)] and concentrated again. This procedure was repeated two times. The obtained residue was dissolved in CHCI3 and the solution cooled to [0C.] A solution of 0.865 [G] (0.0062 mol) of (3R)-N-methylquinuclidin-3-amine (Intermediate I-4) in 10 ml of [CHC13] was added. The mixture was allowed to warm to room temperature under stirring. After 4 hours at this temperature, the reaction mixture was treated with [K2CO3] (saturated solution) and the aqueous phase was extracted with CHC13. The organic solutions were combined and washed with [K2CO3] (saturated solution) and water, dried over [NA2SO4] filtered and concentrated to dryness. The obtained residue was purified by column chromatography [(SILICA GEL, CHCI3] : NH40H 99: [1 # CHCL3 ]: MeOH: NH4OH 98: 2: 1 as eluent) to yield 900 mg (50%) of the title product. MS [[M+1] +] : 349 'H-RMN (400 MHz, [60C,] [CECI3)] : [8] 7.26-7. 19 (m, 4H), 7.10-7. 01 (m, 4H), 5.51 (s, [1 H),] 4.18 (broad [MULTIPLET, 1 H),] 2.92 (s, 3H), 2.85-2. 40 (m, 6H), 1.85-1. 20 (m, 5H).

Reference： [1]Patent: WO2004/5285,2004,A1 .Location in patent: Page 18; 42-43

26
[ 82-07-5 ]
[ 627-30-5 ]
[ 1048693-37-3 ]

Yield	Reaction Conditions	Operation in experiment
81%	With sulfuric acid; In 1,4-dioxane; at 20 - 125℃; for 24h;	[0058]Step_4: Synthesis of 3-chloropropyl-9H-xanthene-carboxylate (CnHuClOi).; [0059] Structure:[0060] 9-Xanthene carboxylic acid (20-g) was dissolved in 90-ml absolute dioxane. This was followed by the addition of 15.83-g of l-Cl-3-propanol dissolved in 20-ml dioxane <n="17"/>and then by the drop-wise (over about 10 min period) addition of 14-ml of sulfuric acid (H2SO4) at room temperature during continuous stirring. The mixture was kept in an oil bath (120-1250C) under gentle reflux for 24 hours. After cooling down to room temperature, the mixture was poured into 300-ml ice-cold distilled water followed by extraction with 3 x 100-ml of diethylether. The combined diethylether phase was sequentially washed with 2 x 100-ml distilled water, 4 x 150-ml of 3% ice-cold sodium carbonate (Na2COs) solution, and 150-ml of saturated sodium chloride (NaCl) solution. The diethylether phase was dried on water-free sodium sulfate (Na2SO4) followed by the removal of solvent by distillation. The resulting dark brown oily material still contained some l-Cl-3-propanol that was removed under vacuum. The yield was 81%; purity -99%. [0061]
81%	With sulfuric acid; In 1,4-dioxane; at 120 - 125℃; for 24.16h;Heating / reflux;	9-Xanthene carboxylic acid (20-g) was dissolved in 90-ml absolute dioxane. This was followed by the addition of 15.83-g of 1-Cl-3-propanol dissolved in 20-ml dioxane and then by the drop-wise (over about 10 min period) addition of 14-ml of sulfuric acid (H2SO4) at room temperature during continuous stirring. The mixture was kept in an oil bath (120-125 C.) under gentle reflux for 24 hours. After cooling down to room temperature, the mixture was poured into 300-ml ice-cold distilled water followed by extraction with 3×100-ml of diethylether. The combined diethylether phase was sequentially washed with 2×100-ml distilled water, 4×150-ml of 3% ice-cold sodium carbonate (Na2CO3) solution, and 150-ml of saturated sodium chloride (NaCl) solution. The diethylether phase was dried on water-free sodium sulfate (Na2SO4) followed by the removal of solvent by distillation. The resulting dark brown oily material still contained some 1-Cl-3-propanol that was removed under vacuum. The yield was 81%; purity99%.

Reference： [1]Patent: WO2008/105872,2008,A1 .Location in patent: Page/Page column 15-16
[2]Patent: US2008/207738,2008,A1 .Location in patent: Page/Page column 9

27
[ 82-07-5 ]
[ 1749-08-2 ]
[ 1150619-71-8 ]

Yield	Reaction Conditions	Operation in experiment
86%	With acetic anhydride; dimethyl sulfoxide; triethylamine; In dichloromethane; at 20℃;	General procedure: Ac2O (1.5 mmol) was added to a solution of substitutedacetic acid (1.5 mmol), Schiff base (1.0 mmol), DMSO (1.5 mmol), and Et3N(5.0 mmol) in dry CH2Cl2 (10 mL) at room temperature, and the mixture wasstirred overnight. The mixture was washed successively with saturatedNaHCO3 (15 mL) and brine (15 mL). The organic layer was dried (Na2SO4),filtered and the solvent was removed under reduced pressure. The crude residue was purified by crystallization from EtOAc.
85%	With 2,2,4,4,6,6-hexachloro-1,3,5-triaza-2,4,6-triphosphorine; triethylamine; In dichloromethane; at 20℃;	General procedure: 4.2. A phosphonitrilic chloride (0.5 mmol) was added to a solution of the substituted acetic acid (1.5 mmol), the Schiff base (1.0 mmol), and Et3N (5.0 mmol) in dry CH2Cl2 (15mL) at room temperature and the mixture was stirred overnight. The mixture was washed successively with saturated NaHCO3 (15 mL) and brine (15 mL). The organic layer was dried (Na2SO4), filtered, and the solvent was removed under reduced pressure to give the crude products. beta-Lactams 5a-u, 7a-d, 11a-c, 17a-d were purified by crystallization from ethyl acetate, beta-lactams 9a-c were purified by crystallization from 96% ethanol, beta-lactams 13a-c by short column chromatography (hexane/EtOAc 7:3), and beta-lactams 15a-c by short column chromatography (hexane/EtOAc 9:1).
79%		General procedure: To a stirred solution of CDMT (1.5 mmol) in dry CH2Cl2(15 mL), N-methylmorpholine (NMM) (6.0 mmol) was added dropwise and allowed to stir for 10 min. To the white suspension containing DMTMM salt, the Schiff base (1.0mmol) and the carboxylic acid (1.5 mmol) were added and the mixture was stirred overnight. The mixture was washed successively with saturated NaHCO3 (15 mL) and brine (15mL), dried with Na2SO4 and concentrated in vacuo. 2-azetidinones 3a-k, 3n-o were purified by crystallizationfrom EtOAc and 2-azetidinones 3l-m by short column chromatographyon silica gel

Reference： [1]Tetrahedron Letters,2014,vol. 55,p. 5354 - 5357
[2]Journal of Heterocyclic Chemistry,2017,vol. 54,p. 1161 - 1166
[3]Bulletin of the Chemical Society of Japan,2012,vol. 85,p. 360 - 368
[4]Tetrahedron,2013,vol. 69,p. 6620 - 6626
[5]Tetrahedron,2009,vol. 65,p. 2927 - 2934
[6]Letters in Organic Chemistry,2015,vol. 12,p. 44 - 49
[7]Tetrahedron,2010,vol. 66,p. 5017 - 5023

28
[ 82-07-5 ]
[ 15484-92-1 ]
[ 1150619-76-3 ]

Reference： [1]Tetrahedron,2009,vol. 65,p. 2927 - 2934
[2]Tetrahedron,2010,vol. 66,p. 5017 - 5023

29
[ 82-07-5 ]
[ 15485-31-1 ]
[ 1150619-77-4 ]

Reference： [1]Bulletin of the Chemical Society of Japan,2012,vol. 85,p. 360 - 368
[2]Tetrahedron,2010,vol. 66,p. 5017 - 5023
[3]Tetrahedron,2009,vol. 65,p. 2927 - 2934

30
[ 82-07-5 ]
[ 6309-32-6 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 5076 - 5092

31
[ 82-07-5 ]
[ 1251936-31-8 ]
[ 1251936-36-3 ]

Reference： [1]Molecules,2010,vol. 15,p. 515 - 531

32
[ 82-07-5 ]
[ 100-46-9 ]
[ 349401-26-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 9H-Xanthene-9-carboxylic acid (10 g, 44.2 mmol) in CH2CI2 (100 ml_), 2- ethoxy-1-ethoxycarbonyl-1,2-dihydrochinolin (16.4 g, 66 mmol) and after 30 min benzylamine (19.3 mL, 177 mmol) are added. The mixture is stirred at room temperature overnight. The mixture is washed with aqueous 1 N HCI, saturated aqueous NaHCO3 and brine. The organic layer is dried over Na2SO4, filtered and concentrated under reduced pressure to give a solid. Ethyl acetate is added to the solid, and the suspension is stirred for 30 min, filtered, washed with ethyl acetate and dried under vacuum overnight to give the title compound as a white solid. MS (LC-MS): 316 [M+H]+; TLC, Rf (hexane/AcOEt 1/1) = 0.75.

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2196 - 2206
[2]Patent: WO2006/117183,2006,A1 .Location in patent: Page/Page column 72-73

33
[ 82-07-5 ]
[ 108764-49-4 ]
[ 1344727-69-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine; p-toluenesulfonyl chloride; In dichloromethane; at 20℃; for 15h;	General procedure: A mixture of the previous crude Schiff base, triethylamine (5.00 mmol), <strong>[82-07-5]9H-xanthen-9-carboxylic acid</strong> or phenoxyacetic acid (1.50 mmol) and tosyl chloride (1.50 mmol) in dry CH2Cl2 (15 mL) was stirred at room temperature for 15 h. Then it was washed with HCl 1 N (20 mL), saturated NaHCO3 (20 mL) and brine (20 mL). The organic layer was dried (Na2SO4), filtered and the solvent was evaporated to give the product as a crystal, which was then purified by recrystallization from ethanol.