Name: 990-91-0|Tetrabenzyl diphosphate|99%
Brand: Ambeed
SKU: A794596
Rating: 91 (35 reviews)

1
[ 1623-08-1 ]
[ 990-91-0 ]

Yield	Reaction Conditions	Operation in experiment
96%	With dicyclohexyl-carbodiimide In Isopropyl acetate at 0 - 6℃; for 1.5h; Inert atmosphere;
95%	With N,N-dicyclohexylurea In toluene at 20℃; for 5h;
91%	With dicyclohexyl-carbodiimide In Isopropyl acetate at 3℃; for 0.916667 - 1.08333h;	1 A 12 L round-bottomed flask was equipped with an overhead stirrer, thermocouple, N2 inlet, and an addition funnel. The vessel was charged with dibenzyl phosphate (762 g) and isopropyl acetate (3 L). The slurry was cooled to 3+/-3° C. and then the 1.08 M dicyclohexylcarbodiimide (DCC) solution (1.30 L) was added via the addition funnel while maintaining the batch temperature at 3+/-3° C. Typical addition times were between 25-35 minutes and the reaction was typically complete within 30 minutes. The cold slurry was filtered and the dicyclohexylurea waste cake was rinsed (agitated) with isopropyl acetate (3×600 mL). The filtrate and rinses were combined and concentrated in vacuo to a final volume of 1.5 L. The batch was transferred to a 12 round-bottomed flask that was equipped with an overhead stirrer, thermocouple, N2 inlet, and an addition funnel. The batch was diluted with heptane (500 mL) and seeded with 1 mol % of tetrabenzyl pyrophosphate (8 g) to form a seed bed. Heptane (4.0 L) was then added to the stirred slurry at room temperature over 30 minutes. The batch was then cooled to 3+/-3° C. and aged for 1 hour. The slurry was filtered and the filter cake washed with 20% isopropyl acetate/heptane (3×500 mL). The product cake was dried in vacuo and under a blanket of nitrogen overnight at room lemperature. Tetrabenzylpyrophosphate was isolated (671 g, 1.25 mol, after correcting for seed) as a white crystalline solid (91% adjusted yield) which was stored in a freezer.

80%	With Isopropyl acetate; dicyclohexyl-carbodiimide at 0 - 5℃; for 0.5h; Inert atmosphere;	6 Under N2 protection, 7.6 g of dibenzyl phosphate and 30 ml of isopropyl acetate were added to a 250 ml dry three-necked flask. Stirring down to 0 ~ 5 . And then slowly dropping 1.1 M dicyclohexylcarbodiimide 13 ml. The dropping speed was controlled so that the temperature was always maintained at 0 to 5 ° C and the addition was completed in 30 minutes. Filter, remove DCU. The cake was washed with isopropyl acetate, the filtrate and the washings were combined and concentrated to 15 ml under reduced pressure. The mixture was diluted with 10 ml of heptane and then seeded. 40 ml of heptane was added while stirring, and the temperature of the mixture was kept at 0 to 5 ° C and crystallized for 1 hour. The cake was washed with a mixed solution of isopropyl acetate and heptane (1: 5) and dried in vacuo to give 5.7 g of a white solid in 80% yield.
	With pyridine; dicyclohexyl-carbodiimide; benzene
	With thionyl chloride; benzene
	With triethylamine; acetonitrile
	With pyridine; acetonitrile
	With pyridine; chloroform
	With 2,6-dimethylpyridine; nitromethane; cyclopentanone-(<i>O</i>-benzenesulfonyl oxime )
	With pyridine; diethyl ether
	With dicyclohexyl-carbodiimide
250 mg	With dicyclohexyl-carbodiimide In diethyl ether; acetonitrile for 0.25h;
671 g	With dicyclohexyl-carbodiimide In Isopropyl acetate at 3℃; for 0.5h; Inert atmosphere;	1 Example 1 Preparation of tetrabenzyl pyrophosphate (TBPP) Under a nitrogen atmosphere, dibenzyl phosphate (762 g) and isopropyl acetate (3 L) were added to a 12 L round bottom flask, and the slurryCooled to 3 ± 3 ° C and then added to the addition of 1. 08M dicyclohexylcarbodiimide (DCC) solution (1.30L) via an addition funnel whileThe bath temperature is maintained at 3 ± 3 ° C and the addition time is usually 25 to 35 minutes for about 30 minutes. After the reaction is over, it will coolThe slurry was filtered and the dicyclohexyl urea waste cake was washed with (isopropyl acetate) (3 * 600 ml) (stirred). Combine the filtrate and washPolyester solution, concentrated to a final volume of 1. 5L. The mixture was transferred to a 12 L round bottom flask and diluted with heptane (500 ml)And lmol% tetralyl pyrophosphate seed (8 g) was added to form a crystallographic bed. Then to 3 ± 3 ° C and aged for 1 hour. The slurry is overThe filter cake was washed with 20% isopropyl acetate / heptane (3 * 500 ml) and the product cake was dried under vacuum at room temperature under vacuumovernight. The tetramethyl pyrophosphate (671 g, l. 25 mol) was isolated as a white solid which was frozen in a refrigerator.When R is a Q 4 alkyl group, a halogen atom, a cyano group or a nitro group in the compound structure of the formula 6, the preparation method is similar to that of the pyro-Acid tetrabenzyl ester (TBPP).

Reference： [1]Nelson, Todd D.; Rosen, Jonathan D.; Bhupathy; McNamara, James; Sowa, Michael J.; Rush, Chad; Crocker, Louis S.; Conway, Stuart J.; Holmes, Andrew B. [Organic Syntheses, 2003, vol. 80, p. 219 - 226]
[2]Elhalabi, Jordan; Rice, Kevin G. [Carbohydrate Research, 2002, vol. 337, # 21-23, p. 1935 - 1940]
[3]Current Patent Assignee: MERCK & CO INC - US2007/265442, 2007, A1 Location in patent: Page/Page column 5
[4]Current Patent Assignee: BEIJING HUAZHONG SIKANG PHARMACEUTICAL TECHNOLOGY - CN102675369, 2017, B Location in patent: Paragraph 0049-0051
[5]Khorana; Todd [Journal of the Chemical Society, 1953, p. 2257,2259]
[6]Mason; Todd [Journal of the Chemical Society, 1951, p. 2267,2270]
[7]Corby et al. [Journal of the Chemical Society, 1952, p. 1234,1239]
[8]Khorana; Todd [Journal of the Chemical Society, 1953, p. 2257,2259]
[9]Smith et al. [Journal of the American Chemical Society, 1958, vol. 80, p. 6204,6206, 6212]
[10]Kenner et al. [Journal of the Chemical Society, 1956, p. 1231,1235]
[11]Khorana; Todd [Journal of the Chemical Society, 1953, p. 2257,2259]
[12]Cramer,F. [Angewandte Chemie, 1960, vol. 72, p. 236 - 249]
[13]Vieira de Almeida, Mauro; Dubreuil, Didier; Cleophax, Jeannine; Verre-Sebrie, Catherine; Pipelier, Muriel; Prestat, Guillaume; Vass, Georges; Gero, Stephane D. [Tetrahedron, 1999, vol. 55, # 23, p. 7251 - 7270]
[14]Current Patent Assignee: BRIGHTGENE BIO MEDICAL TECHNOLOGY CO LTD - CN106146559, 2016, A Location in patent: Paragraph 0042; 0043

2
[ 1080-12-2 ]
[ 990-91-0 ]
[ 141843-89-2 ]

Reference： [1]Synthetic Communications,1992,vol. 22,p. 923 - 931

3
[ 990-91-0 ]
[ 135575-42-7 ]
C₆₄H₈₉N₈O₂₂P [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 194 - 198

4
[ 990-91-0 ]
[ 134098-64-9 ]
[ 153910-63-5 ]

Yield	Reaction Conditions	Operation in experiment
100%		The product of Example 94C (1.70 g, 5.272 mmol) was treated with solid potassium tert-butoxide (0.685 g, 5.799 mmol)in tetrahydrofuran (90 mL) at 60 for 5 minutes followed by tetrabenzyl pyrophosphate (3.123 g, 5.799 mmol) for one additional hour. Upon cooling the resulting thick white reaction mixture was diluted with hexanes (125 mL), vacuum filtered and the filtrate was concentrated by rotary evaporation. Purification of the residue by silica gel flash chromatography eluting with 20:80 ethyl acetate/hexanes afforded the title compound as a colorless oil (3.07 g, 5.27 mmol, quantitative). 1H NMR (300 MHz, CHLOROFORM-D) delta ppm -0.07 (s, 6 H) 0.82 (s, 9 H) 1.51 (s, 6 H) 2.07 (t, J=7.35 Hz 2 H) 2.16 (s, 3 H) 2.49 (s, 3 H) 3.47 (t, J=7.35 Hz, 2 H) 5.10 (d, J=8.09 Hz, 4 H) 6.70 (s, 1 H) 7.08 (s, 1 H) 7.27 - 7.38 (m, 10 H). MS (ESI+) m/z 583 (M+H)+, 605 (M+Na)+.
87.2%		Weigh compound 2c (0.252 g 0.78 mmol) dissolved in 20 ml of fresh THF solution in a 100 ml three-necked bottlePotassium tert-butoxide (0.1 g 0.86 mmol) was added to the flask with stirring and the solution was blue. The oil bath was heated to 60C and the solution changed from blue to yellow after refluxing for about 5 minutes. Tetrabenzyl pyrophosphate (0.463 g, 0.86 mmol) was added while hot, stirring was continued and a milky white precipitate formed. The reaction was continued under reflux for 1 hour. TLC followed the reaction (petroleum ether:ethyl acetate = 3:2). The reaction was stopped and the mixture was cooled. After cooling to room temperature, 30 ml of petroleum ether was added and filtered to remove insolubles. The filtrate was light yellow. The solvent was removed under reduced pressure to give a yellow oil. Purification by column chromatography (eluent: ethyl acetate:petroleum ether=1:3) and evaporation of the solvent gave a pale yellow oil which was dried under vacuum (40 C.) and weighed to give 0.394 g. 87.2%.
43.8%	With potassium tert-butylate; In tetrahydrofuran; at 60℃;	Preparation 3 C: Dibenzyl 2-(4-Qert-butyldimethylsilyloxy)-2-methylbutan-2-yl)-3 ,5 - dimethyiphenyl phosphate [00178j To a stirred solution of Preparation 3B (0.6 g, 1.860 mmol) and potassium 2- methylpropan-2-olate (0.230 g, 2.046 mmol) in THF (6 mL), was added tetrabenzyl diphosphate (1.102 g, 2.046 mmol) and the reaction mixture was allowed to heated at 60C overnight. The reaction mixture was then concentrated under reduced pressure, diluted with EtOAC, and washed with brine (2x10 mL). The organic layer was driedover Na2SO4, filtered and concentrated in vacuo. The residue obtained was purified bysilica gel chromatography (Si02, 20% EtOAc in hexane) to afford Preparation 3C (0.475g, 0.8 15 mmol, 43.8% yield) as a pale yellow liquid. ?H NMR (400 MHz, CHC13-d) oeppm 7.30-7.36 (m, 1OH) 7.09-7.12 (m, 1H) 6.70-6.74 (m, 1H) 5.12 (d, J=8.28 Hz, 4H)3.49 (t, J7.40 Hz, 2H) 2.51 (s, 3H) 2.18 (s, 3H) 2.10 (t, J=7.40 Hz, 2H) 1.53 (s, 6H)0.83-0.85 (m, 9H),) 0.03 (s, 6H).

In N,N-dimethyl-formamide; mineral oil;

EXAMPLE 5 1-O-t-Butyldimethylsilyl-3-(2'-dibenzylphosphonooxy-4',6'-dimethylphenyl)-3,3-dimethylpropanol (VIa) STR29 Sodium hydride (60% in mineral oil, 860 mg, 21.5 mmol, 1.2 eq.) was washed with hexanes, dried under nitrogen and suspended in anhydrous DMF (70 mL). To this suspension was added compound Va (5.8 g, 18 mmol), and the mixture was stirred in an oil bath at 65 C. for 5 min. To this warm reaction mixture was added tetrabenzylpyrophosphate (XXIVa) (14.5 g, 26.93 mmol, 1.5 eq.) all at once. The reaction mixture was continued to be stirred at 65 C. for 10 min. Subsequently, it was diluted with EtOAc (300 mL), washed with brine (4*100 mL) and dried over anhydrous sodium sulfate. It was filtered and the filtrate was concentrated in vacuo to obtain compound VIa as a crude product which was purified on a silica gel column.

Reference： [1]Patent: WO2008/133753,2008,A2 .Location in patent: Page/Page column 136
[2]Journal of Organic Chemistry,1996,vol. 61,p. 8636 - 8641
[3]Patent: CN104892668,2017,B .Location in patent: Paragraph 0033; 0034; 0035
[4]Patent: WO2014/47391,2014,A1 .Location in patent: Paragraph 00178
[5]Patent: US5272171,1993,A

5
[ 990-91-0 ]
[ 170729-80-3 ]
[ 265121-01-5 ]

Yield	Reaction Conditions	Operation in experiment
81.1%		Add 300 ml of tetrahydrofuran to the reaction flask in turn,14.0g <strong>[170729-80-3]aprepitant</strong>,22.3 g of tetrabenzyl pyrophosphate,Nitrogen protection,Cool down to 0 ~ 10 C.A temperature control of 0 to 10 C was added to 33.6 kg of sodium hexamethyldisilazane solution.Plus,The reaction was kept for 1 hour.The reaction is quenched with saturated sodium bicarbonate solution.Extraction with methyl tert-butyl ether.The organic layer was respectively treated with 0.5 M potassium hydrogen sulfate solution,Saturated sodium bicarbonate solution,Washed with saturated sodium chloride solution,Dry over anhydrous sodium sulfate.filter,And concentrated to give a yellow oil.Add 300ml of cyclohexane,Stir at 5 to 15 C for 2 to 3 hours.filter,The filter cake is dried in vacuum for 2 to 3 hours.Obtained a white solid of 16.9 g,The yield was 81.1%.
	With sodium hexamethyldisilazane; In tetrahydrofuran; at -5 - 5℃; for 1h;	A 12 L round-bottomed flask was equipped with an overhead stirrer, a thermocouple and a N2 inlet. The vessel was charged with <strong>[170729-80-3]aprepitant</strong>, 5-[[2(R)-[1(R)-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3(S)-(4-fluorophenyl)-4-morpholinyl]methyl]-1,2-dihydro-3H-1,2,4-triazol-3-one (300 g), tetrabenzyl pyrophosphate (393 g), and 3.85 L of dry THF. The batch was then cooled under N2 to an internal temperature of between -5 and 5 C. NaHMDS (1.37 L of a 1.0 M solution in THF) was added via an addition funnel at such a rate that the internal temperature remained <5 C. Typical addition times were 25-35 minutes and the reaction was typically complete in 60 minutes. Upon completion, the reaction was poured into a rapidly stirred mixture of t-butyl methyl ether (10.4 L) and saturated sodium bicarbonate (10.4 L). The two phase system was separated and the organic layer washed with saturated sodium bicarbonate (1×10.4 L), 10% sodium bisulfate (1×5.2 L) and water (2×5.2 L). The batch was concentrated in vacuo (100 torr) to approximately half its original volume and then solvent switched to methanol (the final batch volume was 3.0 L). The internal batch temperature during the solvent switch was maintained at <25 C. This solution was transferred to a 5 L round-bottomed flask and heated to 45 C. while stirring under nitrogen. After 30 minutes, mono-O-benzylphosphate (3.0 g) was added and a seed bed should persist. The slurry was aged 18 hours at 45 C. The slurry was allowed to cool to room temperature and then aged one hour. The slurry was filtered through a sintered glass funnel and washed with methanol (2×1.2 L). The wet cake was dried in vacuo at room temperature, yielding 307 g (78%, adjusted for seed) mono-O-benzylphosphate intermediate as a white crystalline solid.
		Example 1Preparation of Dibenzylester Fos<strong>[170729-80-3]aprepitant</strong>250 ml of tetrahydrofuran (THF), 10 gm of <strong>[170729-80-3]aprepitant</strong> and 14 gm of tetrabenzylpyrophosphate were charged into a clean and dry 4 neck round bottom flask. The reaction mixture was cooled to about -20 C. 47 ml of 1.0M sodium bis-(trimethylsilyl)amide in THF was added at about -20 C. over about 3 hours. The resultant reaction mixture was stirred for about 30 minutes. After completion of the reaction, the reaction mass was quenched by adding 250 ml of saturated sodium bicarbonate solution. 250 ml of isopropyl ether was charged and stirred for about 15 minutes. Organic and aqueous layers were separated and the organic layer washed with 250 ml of 0.5 M potassium hydrogen sulfate solution. Organic and aqueous layers were separated and the organic layer washed with 250 ml of saturated sodium bicarbonate solution. Organic and aqueous layers were separated and the organic layer was washed with 250 ml of purified water. Organic and aqueous layers were separated and the organic layer was dried over anhydrous sodium sulfate. The organic layer was distilled completely under vacuum to afford the residue. To the residue 30 ml of ethyl acetate was charged and the suspension was stirred for about 30 minutes to get a clear solution. 100 ml of cyclohexane was charged and stirred for about 2 hours. The separated solid was filtered and the solid was washed with cyclohexane. The solid (Formula (II)) obtained was dried at about 30 C. under vacuum for about 1 hour to yield 10 gm of the title compound.Purity by HPLC: 93.74% with monobenzyl fos<strong>[170729-80-3]aprepitant</strong> (III): 1.39% and <strong>[170729-80-3]aprepitant</strong>: 1.0%, other unknown impurities: 3.83%.

	With sodium hexamethyldisilazane; In tetrahydrofuran; at 0 - 5℃; for 1.25h;Inert atmosphere;	<strong>[170729-80-3]Aprepitant</strong> (50 gm), tetrabenzyl pyrophosphate (75 gm) and teterahydrofuran (635 ml) were added under nitrogen atmosphere at room temperature. The contents were then cooled to 0 to 5C and then added sodium hexamethyldisilazane (266.6 ml) slowly for 45 minutes. The reaction mass was stirred for 30 minutes at 0 to 5C and then added sodium bicarbonate solution (8%, 1700 ml) and methyl tert-butyl ether (1700 ml) at room temperature. The layers were separated and the organic layer was washed with saturated sodium hydrogen sulfite solution. Again the layers were separated and the organic layer was washed with water. The organic layer was dried with sodium sulfate and the solvent was distilled off under vacuum at 30 to 35C to obtain 68 gm of dibenzyl fos<strong>[170729-80-3]aprepitant</strong>.
190 g	With water; sodium hydride; In tetrahydrofuran; mineral oil; at 8 - 15℃;Inert atmosphere;	37.50 gm of sodium hydride (60% disperse in oil) was added in 4-5 equal lots to a solution of 150gm of <strong>[170729-80-3]aprepitant</strong> and 218gm of tetrabenzyl pyrophosphate in mixture of 3000ml tetrahydrofuran and 3ml water (0.10% w/v) under nitrogen atmosphere at about 8C-15C. The reaction mass was stirred for about 5-15 minutes, then ethyl acetate and methylene dichloride was added to reaction mass at about 0C to 5C. The reaction mass was stirred for about 5 minutes and organic layer was washed with 10% aqueous sodium bicarbonate solution followed by aqueous sodium chloride solution. The organic layer was dried over sodium sulphate, distilled out solvent and degassed. Cyclohexane was added in solution of degassed mass in ethyl acetate at 25 to 30C to obtain a white solid. The slurry mass was stirred, filtered and dried at about 30C. Crude product obtained further purified by ethyl acetate and cyclohexane to yield pure titled compound. Dry wt: 190gm. Purity: 99.80%; <strong>[170729-80-3]Aprepitant</strong> (Formula III): Not detected; Impurity F: Not detected.

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 1234 - 1241
[2]Patent: CN108948080,2018,A .Location in patent: Paragraph 0025; 0026
[3]Patent: US2007/265442,2007,A1 .Location in patent: Page/Page column 5-6
[4]Patent: US2011/130366,2011,A1 .Location in patent: Page/Page column 9
[5]Patent: WO2012/164576,2012,A2 .Location in patent: Page/Page column 5
[6]Patent: WO2018/211410,2018,A1 .Location in patent: Page/Page column 13-15

6
[ 990-91-0 ]
[ 170729-80-3 ]
[ 265121-01-5 ]
C₄₄H₄₁F₇N₄O₉P₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 1234 - 1241

7
[ 990-91-0 ]
[ 202821-81-6 ]
[ 233676-36-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In tetrahydrofuran
	In tetrahydrofuran	2.A Step A. Step A. 3-[(5-Chloro-2-[[bis[phenylmethyl]phosphono]oxy]phenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one STR17 To a solution of 0.68 g (1.9 mmol) of 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one in 15 mL of THF cooled in an ice bath was added 90 mg (2.2 mmol) of 60% sodium hydride. After stirring for 5 minutes, 1.0 g (1.9 mmol) of tetrabenzylpyrophosphate (purchased from Aldrich chemical company) was added. The ice bath was removed and stirring was continued for 1 hr, after which time the mixture became very viscous. Stirring was discontinued, and the reaction was allowed to stand for 1 hr. The solid was filtered and washed with THF. The filtrate was evaporated and the residue was triturated with acetonitrile. The solids were filtered and the filtrate was concentrated and purified on a flash chromatography column, eluding with hexane/ethyl acetate 3:1 to give 0.97 g of 3-[(5-chloro-2-[[bis[phenylmethyl]phosphono]oxy]phenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one as a clear, colorless oil which partially solidified upon standing. MS 631 (MH+). 1 H NMR (300 MHz; CDCl3) δ7.88 (2H, d, J=8.1 Hz), 7.67 (2H, d J=8.1 Hz), 7.3-7.2 (13H, m), 5.17 (2H, s), 5.14 (2H, s), 4.90 (2H, s).
	In tetrahydrofuran	2.A Step A. Step A. 3-[(5-Chloro-2-[[bis[phenylmethyl]phosphono]oxy]Dhenyl)-methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3 H)-one To a solution of 0.68 g (1.9 mmol) of 3-[(5-chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one in 15 mL of THF cooled in an ice bath was added 90 mg (2.2 mmol) of 60% sodium hydride. After stirring for 5 minutes, 1.0 g (1.9 mmol) of tetrabenzylpyrophosphate (purchased from Aldrich chemical company) was added. The ice bath was removed and stirring was continued for 1 hr, after which time the mixture became very viscous. Stirring was discontinued, and the reaction was allowed to stand for 1 hr. The solid was filtered and washed with THF. The filtrate was evaporated and the residue was triturated with acetonitrile. The solids were filtered and the filtrate was concentrated and purified on a flash chromatography column, eluding with hexane/ethyl acetate 3:1 to give 0.97 g of 3-[(5-chloro-2-[[bis[phenylmethyl]phosphono]oxy]phenyl]methyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2(3H)-one as a clear, colorless oil which partially solidified upon standing. MS 631 (MH+). 1H NMR (300 MHz; CDCl3) δ 7.88 (2H, d, J=8.1 Hz), 7.67 (2H, d J= 8.1 Hz), 7.3-7.2 (13H, m), 5.17 (2H, s), 5.14 (2H, s), 4.90 (2H, s).

Reference： [1]Hewawasam, Piyasena; Ding, Min; Chen, Nathan; King, Dalton; Knipe, Jay; Pajor, Lorraine; Ortiz, Astrid; Gribkoff, Valentin K.; Starrett, John [Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 10, p. 1695 - 1698]
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US5939405, 1999, A
[3]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - EP1056754, 2003, B1

8
[ 2163-42-0 ]
[ 990-91-0 ]
3-(dibenzyl)phosphoryloxy-2-methyl-1-propanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere; chemoselective reaction;	General procedure for the phosphorylation of diols. General procedure: The diol (0.49 mmol) was dissolved in 1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to the solution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol). Ti(OtBu)4 (19 μL, 0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. To quench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2 mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate was concentrated under reduced pressure. The crude product was purified using silica gel chromatography.
84%	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere;	General Procedure for the Phosphorylation of Diols General procedure: The diol (0.49 mmol) was dissolved in1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to thesolution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol;). Ti(OtBu)4 (19 μL,0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. Toquench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate wasconcentrated under reduced pressure. The crude product was purified using silica gelchromatography.
74%	With tetrahexylammonium iodide; silver(l) oxide In dichloromethane at 20℃; for 20h;

54%

With titanium(IV) isopropylate; (R)-1,1'-Bi-2-naphthol; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 16h; Inert atmosphere; enantioselective reaction;

Reference： [1]Coppola, Kyle A.; Testa, Joseph W.; Allen, Emily E.; Sculimbrene, Bianca R. [Tetrahedron Letters, 2014, vol. 55, # 30, p. 4203 - 4206]
[2]Coppola, Kyle A.; Testa, Joseph W.; Allen, Emily E.; Sculimbrene, Bianca R. [Tetrahedron Letters, 2014, vol. 55, # 30, p. 4203 - 4206]
[3]Takeda, Shuzo; Chino, Masao; Kiuchi, Masatoshi; Adachi, Kunitomo [Tetrahedron Letters, 2005, vol. 46, # 31, p. 5169 - 5172]
[4]Ouellette, Erik T.; Lougee, Marshall G.; Bucknam, Andrea R.; Endres, Paul J.; Kim, John Y.; Lynch, Emma J.; Sisko, Elizabeth J.; Sculimbrene, Bianca R. [Journal of Organic Chemistry, 2021, vol. 86, # 11, p. 7450 - 7459]

9
[ 10210-17-0 ]
[ 990-91-0 ]
3-[4-(dibenzyl)phosphoryloxy]phenyl-1-propanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With tetrahexylammonium iodide; silver(l) oxide In dichloromethane at 20℃; for 20h;

Reference： [1]Takeda, Shuzo; Chino, Masao; Kiuchi, Masatoshi; Adachi, Kunitomo [Tetrahedron Letters, 2005, vol. 46, # 31, p. 5169 - 5172]

10
[ 990-91-0 ]
[ 126-30-7 ]
3-(dibenzyl)phosphoryloxy-2,2-dimethyl-1-propanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere; chemoselective reaction;	General procedure for the phosphorylation of diols. General procedure: The diol (0.49 mmol) was dissolved in 1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to the solution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol). Ti(OtBu)4 (19 μL, 0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. To quench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2 mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate was concentrated under reduced pressure. The crude product was purified using silica gel chromatography.
90%	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere;	General Procedure for the Phosphorylation of Diols General procedure: The diol (0.49 mmol) was dissolved in1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to thesolution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol;). Ti(OtBu)4 (19 μL,0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. Toquench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate wasconcentrated under reduced pressure. The crude product was purified using silica gelchromatography.
76%	With tetrahexylammonium iodide; silver(l) oxide In dichloromethane at 20℃; for 20h;

Reference： [1]Coppola, Kyle A.; Testa, Joseph W.; Allen, Emily E.; Sculimbrene, Bianca R. [Tetrahedron Letters, 2014, vol. 55, # 30, p. 4203 - 4206]
[2]Coppola, Kyle A.; Testa, Joseph W.; Allen, Emily E.; Sculimbrene, Bianca R. [Tetrahedron Letters, 2014, vol. 55, # 30, p. 4203 - 4206]
[3]Takeda, Shuzo; Chino, Masao; Kiuchi, Masatoshi; Adachi, Kunitomo [Tetrahedron Letters, 2005, vol. 46, # 31, p. 5169 - 5172]

11
[ 990-91-0 ]
[ 103914-44-9 ]
[ 1032315-67-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: 6-fluoro-2-phenylquinolin-4(1H)-one With sodium hydride In tetrahydrofuran at 0℃; for 1h; Stage #2: dibenzyl [[bis(benzyloxy)phosphoryl]oxy]phosphonate In tetrahydrofuran at 0℃; for 0.333333h;	3 Example 3; Dibenzyl 6-fluoro-2-phenylquinolin-4-yl-phosphate (I-3-a); Sodium hydride (13.7 mg, 0.57 mmol) was added at O0C to a stirred solution of compound I-3 (55.0 mg, 0.23 mmol) in dry tetrahydrofuran (10 ml). After 1 h, tetrabenzyl pyrophosphate (100 mg, 0.19 mmol) was added and the stirring was continued for 20 min.The mixture was filtered, and the filtrate was concentrated under vacuum at a temperature below 35°C. The residue was dissolved in dichloromethane, washed with an aqueous solution of sodium hydrogen carbonate, dried over MgSO4 and concentrated under vacuum to give I-3-a as a colorless oil compound (84.4 mg, 89 %). 1H-NMR (DMSO-c/6, 200 MHz): δ 8.07-8.14 (m, 1 H, H-8), 7.92-7.97 (m,2H, H-21 ,H-6'), 7.67-7.77 (m, 2H, H-3', H-51) , 7.40-7.50 (m, 1 OH, Ph), 5.31 (s, 2H, -CH1-Ph), 5.27(s, 2H, -CH2-Ph)MS (m/z) 500 (ES+) Anal, calcd for C29H23FNO6P: C, 69.74; H1 4.64; N, 2.80. Found: C.69.75 ;H, 4.60; N, 2.81.

Reference： [1]Current Patent Assignee: CHINA MEDICAL UNIVERSITY TAIWAN - WO2008/70176, 2008, A1 Location in patent: Page/Page column 15

12
[ 990-91-0 ]
[ 170729-80-3 ]
dibenzyl fosaprepitant [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.4%		Process for the Preparation of phosphorylated <strong>[170729-80-3]aprepitant</strong> using NMP and Lithium hydroxide monohydrate.Taken 10 ml of NMP under stirring and added 0.23 gm (5.47 mmole) lithium hydroxide monohydrate at ambient temperature. Added 0.5 gm (0.93 mmole) of <strong>[170729-80-3]aprepitant</strong> and stirred for 30 mins to get clear solution. Added 0.56 gm of (1.04 mmole) tetra benzyl pyrophosphate under stirring. Stirred the clear solution for 30 mins at 25-30C. Monitored reaction progress by HPLC. After completion of reaction (<strong>[170729-80-3]aprepitant</strong> < 0.5 %), cooled the reaction mass to 10- 15 C. Added 20 ml DCM under stirring. Separated the layers. Washed organic layer with (4x 25 ml) water and (2x 10 ml) saturated sodium bi-carbonate solution. Dryed DCM layer over 1.0 gm anhydrous sodium sulphate and concentrated under vacuum at ambient temperature to give yellow colored oil.Yield-0.65gm (87.4% theory).

Reference： [1]Patent: WO2011/45817,2011,A2 .Location in patent: Page/Page column 9-10

13
[ 3360-41-6 ]
[ 990-91-0 ]
[ 136025-58-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h; Inert atmosphere;	4.2 General procedure for the phosphorylation of alcohols with TBPP General procedure: The alcohol (0.49 mmol) was dissolved in 1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to the solution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol). Ti(OtBu)4 (19 μL, 0.049 mmol, 10 mol %) was added and the reaction was stirred for 16 h at room temperature. The solution was then vacuum filtered through a 20:1 Silica/MgSO4 plug and washed with 50 mL of 1:1 EtOAc/petroleum ether. The filtrate was concentrated under reduced pressure and a crude NMR was obtained for conversion. The crude product was purified using silica gel chromatography. See Table 2 for conversion and yield data.

Reference： [1]Fenton, Owen S.; Allen, Emily E.; Pedretty, Kyle P.; Till, Sean D.; Todaro, Joseph E.; Sculimbrene, Bianca R. [Tetrahedron, 2012, vol. 68, # 44, p. 9023 - 9028]

14
[ 106-24-1 ]
[ 990-91-0 ]
geranyldibenzyl phosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h; Inert atmosphere;	4.2 General procedure for the phosphorylation of alcohols with TBPP General procedure: The alcohol (0.49 mmol) was dissolved in 1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to the solution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol). Ti(OtBu)4 (19 μL, 0.049 mmol, 10 mol %) was added and the reaction was stirred for 16 h at room temperature. The solution was then vacuum filtered through a 20:1 Silica/MgSO4 plug and washed with 50 mL of 1:1 EtOAc/petroleum ether. The filtrate was concentrated under reduced pressure and a crude NMR was obtained for conversion. The crude product was purified using silica gel chromatography. See Table 2 for conversion and yield data.

Reference： [1]Fenton, Owen S.; Allen, Emily E.; Pedretty, Kyle P.; Till, Sean D.; Todaro, Joseph E.; Sculimbrene, Bianca R. [Tetrahedron, 2012, vol. 68, # 44, p. 9023 - 9028]

15
[ 107-41-5 ]
[ 990-91-0 ]
2-di(benzyloxy)phosphoryloxy-4-methylpentan-4-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere; chemoselective reaction;	General procedure for the phosphorylation of diols. General procedure: The diol (0.49 mmol) was dissolved in 1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to the solution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol). Ti(OtBu)4 (19 μL, 0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. To quench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2 mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate was concentrated under reduced pressure. The crude product was purified using silica gel chromatography.
85%	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere;	General Procedure for the Phosphorylation of Diols General procedure: The diol (0.49 mmol) was dissolved in1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to thesolution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol;). Ti(OtBu)4 (19 μL,0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. Toquench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate wasconcentrated under reduced pressure. The crude product was purified using silica gelchromatography.

Reference： [1]Coppola, Kyle A.; Testa, Joseph W.; Allen, Emily E.; Sculimbrene, Bianca R. [Tetrahedron Letters, 2014, vol. 55, # 30, p. 4203 - 4206]
[2]Coppola, Kyle A.; Testa, Joseph W.; Allen, Emily E.; Sculimbrene, Bianca R. [Tetrahedron Letters, 2014, vol. 55, # 30, p. 4203 - 4206]

16
[ 1570-95-2 ]
[ 990-91-0 ]
3-di(benzyloxy)phosphoryloxy-2-phenyl-1-propanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere; chemoselective reaction;	General procedure for the phosphorylation of diols. General procedure: The diol (0.49 mmol) was dissolved in 1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to the solution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol). Ti(OtBu)4 (19 μL, 0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. To quench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2 mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate was concentrated under reduced pressure. The crude product was purified using silica gel chromatography.
81%	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere;	General Procedure for the Phosphorylation of Diols General procedure: The diol (0.49 mmol) was dissolved in1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to thesolution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol;). Ti(OtBu)4 (19 μL,0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. Toquench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate wasconcentrated under reduced pressure. The crude product was purified using silica gelchromatography.

Reference： [1]Coppola, Kyle A.; Testa, Joseph W.; Allen, Emily E.; Sculimbrene, Bianca R. [Tetrahedron Letters, 2014, vol. 55, # 30, p. 4203 - 4206]
[2]Coppola, Kyle A.; Testa, Joseph W.; Allen, Emily E.; Sculimbrene, Bianca R. [Tetrahedron Letters, 2014, vol. 55, # 30, p. 4203 - 4206]

17
[ 10210-17-0 ]
[ 990-91-0 ]
3-[4-(dibenzyl)phosphoryloxy]phenyl-1-propanol [ No CAS ]
3-(4-hydroxyphenyl)-1-propyl dibenzyl phosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere; Overall yield = 84 %; chemoselective reaction;	General procedure for the phosphorylation of diols. General procedure: The diol (0.49 mmol) was dissolved in 1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to the solution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol). Ti(OtBu)4 (19 μL, 0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. To quench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2 mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate was concentrated under reduced pressure. The crude product was purified using silica gel chromatography.

Reference： [1]Coppola, Kyle A.; Testa, Joseph W.; Allen, Emily E.; Sculimbrene, Bianca R. [Tetrahedron Letters, 2014, vol. 55, # 30, p. 4203 - 4206]

18
[ 10210-17-0 ]
[ 990-91-0 ]
3-(4-hydroxyphenyl)-1-propyl dibenzyl phosphate [ No CAS ]
C₃₇H₃₈O₈P₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With titanium(IV) tetrabutoxide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere; Overall yield = 84 %;	General Procedure for the Phosphorylation of Diols General procedure: The diol (0.49 mmol) was dissolved in1.0 mL of CH2Cl2. N,N-Diisopropylethylamine (0.130 mL, 0.746 mmol) was added to thesolution, followed by tetrabenzylpyrophosphate (0.320 g, 0.594 mmol;). Ti(OtBu)4 (19 μL,0.049 mmol, 10 mol %) was added and the reaction was stirred for 4 h at room temperature. Toquench the reaction, the crude solution was filtered through a 5 mL plastic syringe containing 2mL of 20:1 Silica/MgSO4 and washed with 60 mL of 75% EtOAc/hexanes. The filtrate wasconcentrated under reduced pressure. The crude product was purified using silica gelchromatography.

Reference： [1]Coppola, Kyle A.; Testa, Joseph W.; Allen, Emily E.; Sculimbrene, Bianca R. [Tetrahedron Letters, 2014, vol. 55, # 30, p. 4203 - 4206]

19
[ 856866-72-3 ]
[ 990-91-0 ]
dibenzyl (R)-[3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl]methyl phosphoric acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%		1.1 g of sodium hydride,50mL dry tetrahydrofuran addedInto a 100 mL round bottom flask,In an ice bath,Under nitrogen protection conditions,A solution of 5 g of a compound of formula II in dry tetrahydrofuran was added dropwise to the reaction flask,After the addition is completed,Warmed to room temperature and stirred for 5 hours;Subsequently, 11 g tetrabenzyl pyrophosphate was added in portionsIn the reaction solution,The reaction was stirred at room temperature for 10 hours.The reaction was complete by TLC.To the reaction mixture was slowly addedIce water quenching reaction,Ethyl acetate extraction,Layered, the organic layer was dried, concentrated,The residue is recrystallized from ethyl acetate / petroleum ether,About 7 g of a light yellow solid was obtained in a yield of 82%.

Reference： [1]Patent: CN104610359,2017,B .Location in patent: Paragraph 0039; 0040; 0041

20
[ 990-91-0 ]
[ 259793-96-9 ]
dibenzyl (3-carbamoyl-5-fluoropyrazin-2-yl) phosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%		In a 10 mL two-necked flask, N, N-dimethylformamide (5 mL) and <strong>[259793-96-9]6-fluoro-3-hydroxypyrazine-2-carboxamide</strong> (200 mg,1.27 mmol) and NaH (60%, 203 mg, 5.08 mmol) was added portionwise under nitrogen atmosphere to the reaction system, followed by stirring for 1 hour. Tetrabenzyl diphosphate (820 mg, 1.52 mmol) was added in portions. Plus continue to room temperature for 3 hours. The solid was filtered off and the crude product purified by medium pressure preparation (mobile phase: CH3CN, H2O, 1% NH4HCO3). The fractions were collected and lyophilized to give 192 mg of product (36% yield) as a yellow solid.

Reference： [1]Patent: CN105884827,2016,A .Location in patent: Paragraph 0073-0076

21
[ 990-91-0 ]
[ 252742-72-6 ]
C₁₇H₁₇ClN₃O₄P [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium tert-butylate; In tetrahydrofuran; at -5℃;	13.35 g (100 mmol) of 3-chloromethyl-1, 2, 4-triazolin-5-one, 64.628 (120 mmol) tetrabenzyl pyrophosphate and 50 ml of THF were added to the reaction flask, stirred well, cooled down to -5 ° C, 24.69 g (220 mmol) of potassium t-butoxide was added, after the addition, continue to stir the reaction, TLC monitor the reaction end point. 300 ml of saturated sodium bicarbonate solution and 300 ml of isopropyl ether were added the reaction solution, stirred for 15 min, and dispense, the organic phase was washed with saturated brine until neutral, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated to dryness, dried in vacuo to give 33.86 g white solid, yield 86percent.

Reference： [1]Patent: CN104650143,2018,B .Location in patent: Paragraph 0037; 0038; 0040; 0041

22
[ 990-91-0 ]
[ 405-05-0 ]
dibenzyl (2-fluoro-4-formylphenyl) phosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In tetrahydrofuran; at 70℃; for 1h;	To a solution of <strong>[405-05-0]3-fluoro-4-hydroxybenzaldehyde</strong> (1 g, 7.1 mmol) in THE (32 mL) was added a 1 M solution of tBuOK in THF (7.6 mL, 7.6 mmol). The mixture was heated to 70 C. and tetrabenzylphosphate was added (4.0 g, 7.4 mmol). After 1 h at 70 C., hexanes was added to the mixture and the contents were filtered. The filtrate was concentrated in vacuo and the resulting residue was purified by silica gel column chromatography (0 to 100% EtOAc in hexanes) to produce dibenzyl (2-fluoro-4-formylphenyl)phosphate. MS: (ES) m/z calculated for C21H18FO5P [M+H]+ 401.1, found 401.1.

Reference： [1]Patent: US2019/300526,2019,A1 .Location in patent: Paragraph 0215; 0256

23
[ 990-91-0 ]
[ 129453-61-8 ]
dibenzyl ((7R,8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-7-(9-((4,4,5,5,5-pentafluoropentyl)sulfinyl)nonyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl) phosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62.99%	Stage #1: fulvestrant With potassium <i>tert</i>-butylate In tetrahydrofuran at 70℃; for 0.0833333h; Stage #2: dibenzyl [[bis(benzyloxy)phosphoryl]oxy]phosphonate In tetrahydrofuran at 70℃; for 18h;	20.1 Step-l: Preparation of dibenzyl ((7R,8R,9S,l3S,l4S, l7S)-l7-hydroxy-l3-methyl-7-(9- ((4.4.5.5.5-pcntafluoropcntyl)sulfinyl)nonyl)-7.8.9.1 1. 12.13. 14.15.16.17-dccahydro-6 /- cyclopenta[a]phenanthren-3-yl) phosphate To a stirred solution of fulvestrant (0.25 g) in tetrahydrofuran (10 ml), potassium tert. Butoxide (0.05 g) was added at room temperature. Reaction mixture was stirred at 70° C for 5 min. Tetrabenzyl pyrophosphate (0.244 g) was added to reaction mixture at 70° C. Reaction mixture was vigorously stirred at 70° C for 18 h. The progress of reaction was monitored by TLC and LCMS. After completion of reaction, reaction mixture was cooled to room temperature and poured into water (50 ml). Reaction mixture was extracted in ethyl acetate (3x25 ml). Combined organic layer was washed with saturated brine solution (50 ml) and dried over anhydrous NaiSOv Organic layer concentrated to provide crude residue. The crude residue was purified by flash chromatography to afford the title compound (0.225 g, 62.99%). (0428) 'H-NMR (400 MHz, DMSO): d 7.384 (s, 10H), 7.291 (d, 1H), 6.921 (d, 1H), 6.827 (s, 1H), 5.168 (s, 2H), 5.148 (s, 2H), 4.559 (s, 1H), 4.534 (s, 1H), 3.558 (m, 2H), 2.891-2.871 (s, 2H), 2.832- (0429) 2.623 (m, 4H), 2.456-2.249 (m, 4H), 1.956-1.801 (m, 5H), 1.694 (s, 1H), 1.632-1.492 (m, 4H), 1.525- 1.102 (m, 22H), 0.865 (dd, 1H) and 0.684 (s, 3H).

Reference： [1]Current Patent Assignee: KASHIV BIOSCIENCES LLC - WO2019/224790, 2019, A2 Location in patent: Page/Page column 57-58

24
[ 115-84-4 ]
[ 990-91-0 ]
dibenzyl (2-ethyl-2-(hydroxymethyl)hexyl) phosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With titanium(IV) isopropylate; (R)-1,1'-Bi-2-naphthol; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 16h; Inert atmosphere; enantioselective reaction;

Reference： [1]Ouellette, Erik T.; Lougee, Marshall G.; Bucknam, Andrea R.; Endres, Paul J.; Kim, John Y.; Lynch, Emma J.; Sisko, Elizabeth J.; Sculimbrene, Bianca R. [Journal of Organic Chemistry, 2021, vol. 86, # 11, p. 7450 - 7459]

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	990-91-0	MDL No. :	MFCD00051941
Formula :	C₂₈H₂₈O₇P₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NSBNXCZCLRBQTA-UHFFFAOYSA-N
M.W :	538.47	Pubchem ID :	563183
Synonyms :

Signal Word:	Danger	Class:	8
Precautionary Statements:	P260-P264-P280-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P363-P405-P501	UN#:	3261
Hazard Statements:	H314	Packing Group:	Ⅱ
GHS Pictogram:

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P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
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

[ CAS No. 990-91-0 ] {[proInfo.proName]}

Quality Control of [ 990-91-0 ]

Related Doc. of [ 990-91-0 ]

Product Details of [ 990-91-0 ]

Safety of [ 990-91-0 ]

Application In Synthesis of [ 990-91-0 ]

[ 990-91-0 ] Synthesis Path-Downstream 1~24

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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