[ CAS No. 5382-77-4 ] {[proInfo.proName]}

Name: 5382-77-4|Diethyl dihydro-2H-pyran-4,4(3H)-dicarboxylate|97%
Brand: Ambeed
SKU: A598114
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Quality Control of [ 5382-77-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 5382-77-4 ]

Product Details of [ 5382-77-4 ]

CAS No. :	5382-77-4	MDL No. :	MFCD01853862
Formula :	C₁₁H₁₈O₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ILUMJWCFQOFDMA-UHFFFAOYSA-N
M.W :	230.26	Pubchem ID :	239606
Synonyms :

Calculated chemistry of [ 5382-77-4 ]

Physicochemical Properties

Num. heavy atoms :	16
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.82
Num. rotatable bonds :	6
Num. H-bond acceptors :	5.0
Num. H-bond donors :	0.0
Molar Refractivity :	56.27
TPSA :	61.83 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.94 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.71
Log Po/w (XLOGP3) :	1.07
Log Po/w (WLOGP) :	0.91
Log Po/w (MLOGP) :	0.62
Log Po/w (SILICOS-IT) :	1.84
Consensus Log Po/w :	1.43

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.55
Solubility :	6.55 mg/ml ; 0.0285 mol/l
Class :	Very soluble
Log S (Ali) :	-1.96
Solubility :	2.52 mg/ml ; 0.011 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.97
Solubility :	2.48 mg/ml ; 0.0108 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.48

Safety of [ 5382-77-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 5382-77-4 ]

* 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 [ 5382-77-4 ]
Downstream synthetic route of [ 5382-77-4 ]

[ 5382-77-4 ] Synthesis Path-Upstream 1~3

1
[ 5382-77-4 ]
[ 40191-32-0 ]

Reference： [1] Helvetica Chimica Acta, 1997, vol. 80, # 5, p. 1528 - 1551

2
[ 5382-77-4 ]
[ 96835-17-5 ]

Yield	Reaction Conditions	Operation in experiment
92%	With lithium iodide In N,N-dimethyl-formamide	1. Alternative Preparation of a Compound of Formula (8) where R ¹ and R ² taken together with the Carbon to which they are attached represent Tetrahydropyran To a solution of tetrahydropyran-4,4-dicarboxylic acid diethyl ester (400 mg, 1.74 mmol) in N,N-dimethylformamide (4 ml), was added lithium iodide (1.16 g, 8.66 mmol), followed by sodium cyanide (94 mg, 1.91 mmol). The mixture was heated at 130°C for 7 hours, 140°C for 25 hours, after which GC analysis indicated the reaction to be >95percent complete. The mixture was partitioned between 33percent diethyl ether/hexanes (100 ml) and brine (25 ml). The organic layer was washed with additional brine (25 ml), dried (MgSO₄) and concentrated in vacuoto afford the tetrahydropyran-4-carboxylic acid ethyl ester (253 mg, 92percent). Note:
92%	With lithium iodide In N,N-dimethyl-formamide	1. To a solution of tetrahydropyran-4,4-dicarboxylic acid diethyl ester (400 mg, 1.74 mmol) in N,N-dimethylformamide (4 mL), was added lithium iodide (1.16 g, 8.66 mmol), followed by sodium cyanide (94 mg, 1.91 mmol). The mixture was heated at 130° C. for 7 hours, 140° C. for 25 hours, after which GC analysis indicated the reaction to be >95percent complete. The mixture was partitioned between 33percent diethyl ether/hexanes (100 mL) and brine (25 mL). The organic layer was washed with additional brine (25 mL), dried (MgSO₄) and concentrated in vacuo to afford the tetrahydropyran-4-carboxylic acid ethyl ester (253 mg, 92percent). Note:

Reference： [1] Patent: EP780386, 1997, A1,
[2] Patent: US5932595, 1999, A,
[3] Patent: US6342639, 2002, B1, . Location in patent: Scheme D

3
[ 5382-77-4 ]
[ 5337-04-2 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: With sodium hydroxide In water at 20℃; for 28 h; Stage #2: With hydrogenchloride In water	Diethyl tetrahydro-2H-pyran-4,4-dicarboxylate (4.04 g, 20 mmol) is suspended in a 30 percent aqueous sodium hydroxide solution (10 mL), and the mixture is stirred at room temperature for 28 hours. The pH value of the reaction solution is adjusted to pH 1 with conc. hydrochloric acid, and the mixture is separated into water and ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, and the solvent is evaporated. Ethyl acetate (30mL) is added to the obtained crude product, and the mixture is washed by repulping, and the resulting solid is collected by filtration, and dried to give tetrahydro-4H-pyran-4,4-dicarboxylic acid (3.19 g, 18.3 mmol, 92 percent). 1H-NMR (DMSO-d6) δ: 1.90 (4H, t, J=5.3Hz), 3.55 (4H, t, J=5.3Hz), 12.93 (2H, s).
90.2%	With potassium hydroxide In ethanol; water	Oxane-4,4-dicarboxylic Acid To a stirred solution of diethyl oxane-4,4-dicarboxylate (40.0 g., 173 mmol) in ethanol (100 mL) was added a solution of potassium hydroxide (21.4 g, 382 mmol) in ethanol (300 mL). After the completion of the addition, the reaction mixture was stirred for 15 min at ambient temperature and then refluxed for 2.5 h. Water (40 mL) was added to the thick, white suspension, and then the solvent was removed by rotary evaporation. Water (40 mL) was added to the remaining residue and the resulting mixture then acidified with concentrated sulfuric acid (20 mL). The acidic solution was extracted with diethyl ether (3*300 mL) and the combined organic layers were dried (Na₂SO₄). Removal of solvent by rotary evaporation yielded the product (27.3 g, 90.2percent yield).
61%	Stage #1: Cooling with ice; Reflux Stage #2: With hydrogenchloride In water	Reference Example 3; Tetrahydro-pyran-4,4-dicarboxylic acid; 6M potassium hydroxide solution (10 mL, 60 mmol) was added to an ice-cooled solution of tetrahydropyran-4,4-dicarboxylic acid diethyl ester (5 g, 21.7 mmol) in ethanol (40 mL) and heated at reflux overnight. The volatiles were evaporated, the residue diluted with water and acidified with conc. hydrochloric acid. The mixture was allowed to stand overnight then extracted with ether (3.x.25 mL). The combined ether layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo to afford tetrahydro-pyran-4,4-dicarboxylic acid (2.3 g, 61percent) as a white solid.

61%

Stage #1: With potassium hydroxide; water In ethanolHeating / reflux
Stage #2: With hydrogenchloride In water

Reference Example 4: Tetrahydro-pyran-4,4-dicarboxylic acid. 6M potassium hydroxide solution (10 mL, 60 mmol) was added to an ice-cooled solution of tetrahydropyran-4,4-dicarboxylic acid diethyl ester (5 g, 21.7 mmol) in ethanol (40 mL) and heated at reflux for overnight. The volatiles were evaporated, the residue diluted with water and acidified with cone, hydrochloric acid. The mixture was allowed to stand overnight then extracted with ether (3 x 25 mL). The combined ether layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo to afford tetrahydro-pyran-4,4-dicarboxylic acid (2.3 g, 61percent) as a white solid.

Reference： [1] Patent: EP1514869, 2005, A1, . Location in patent: Page/Page column 52
[2] Patent: US2004/220214, 2004, A1,
[3] Phosphorus, Sulfur and Silicon and the Related Elements, 1990, vol. 47, # 1 + 2, p. 157 - 164
[4] Helvetica Chimica Acta, 1997, vol. 80, # 5, p. 1528 - 1551
[5] Patent: US2011/9390, 2011, A1, . Location in patent: Page/Page column 14
[6] Patent: WO2008/62182, 2008, A1, . Location in patent: Page/Page column 110-111
[7] Collection of Czechoslovak Chemical Communications, 1932, vol. 4, p. 259,263

[ 5382-77-4 ] Synthesis Path-Downstream 1~36

1
[ 5382-77-4 ]
[ 57-13-6 ]
[ 118802-47-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium isopropylate; isopropyl alcohol Behandeln einer wss. Loesung des Reaktionsprodukts mit wss. Salzsaeure;

Reference： [1]Stanfield; Daugherty [Journal of the American Chemical Society, 1959, vol. 81, p. 5167,5169]

2
[ 5382-77-4 ]
[ 5337-04-2 ]

Yield	Reaction Conditions	Operation in experiment
92%		Diethyl tetrahydro-2H-pyran-4,4-dicarboxylate (4.04 g, 20 mmol) is suspended in a 30 % aqueous sodium hydroxide solution (10 mL), and the mixture is stirred at room temperature for 28 hours. The pH value of the reaction solution is adjusted to pH 1 with conc. hydrochloric acid, and the mixture is separated into water and ethyl acetate. The organic layer is dried over anhydrous sodium sulfate, and the solvent is evaporated. Ethyl acetate (30mL) is added to the obtained crude product, and the mixture is washed by repulping, and the resulting solid is collected by filtration, and dried to give tetrahydro-4H-pyran-4,4-dicarboxylic acid (3.19 g, 18.3 mmol, 92 %). 1H-NMR (DMSO-d6) delta: 1.90 (4H, t, J=5.3Hz), 3.55 (4H, t, J=5.3Hz), 12.93 (2H, s).
90.2%	With potassium hydroxide; In ethanol; water;	Oxane-4,4-dicarboxylic Acid To a stirred solution of diethyl oxane-4,4-dicarboxylate (40.0 g., 173 mmol) in ethanol (100 mL) was added a solution of potassium hydroxide (21.4 g, 382 mmol) in ethanol (300 mL). After the completion of the addition, the reaction mixture was stirred for 15 min at ambient temperature and then refluxed for 2.5 h. Water (40 mL) was added to the thick, white suspension, and then the solvent was removed by rotary evaporation. Water (40 mL) was added to the remaining residue and the resulting mixture then acidified with concentrated sulfuric acid (20 mL). The acidic solution was extracted with diethyl ether (3*300 mL) and the combined organic layers were dried (Na2SO4). Removal of solvent by rotary evaporation yielded the product (27.3 g, 90.2% yield).
61%		Reference Example 3; Tetrahydro-pyran-4,4-dicarboxylic acid; 6M potassium hydroxide solution (10 mL, 60 mmol) was added to an ice-cooled solution of tetrahydropyran-4,4-dicarboxylic acid diethyl ester (5 g, 21.7 mmol) in ethanol (40 mL) and heated at reflux overnight. The volatiles were evaporated, the residue diluted with water and acidified with conc. hydrochloric acid. The mixture was allowed to stand overnight then extracted with ether (3×25 mL). The combined ether layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo to afford tetrahydro-pyran-4,4-dicarboxylic acid (2.3 g, 61%) as a white solid.

61%

Reference： [1]Patent: EP1514869,2005,A1 .Location in patent: Page/Page column 52
[2]Patent: US2004/220214,2004,A1
[3]Phosphorus, Sulfur and Silicon and the Related Elements,1990,vol. 47,p. 157 - 164
[4]Helvetica Chimica Acta,1997,vol. 80,p. 1528 - 1551
[5]Patent: US2011/9390,2011,A1 .Location in patent: Page/Page column 14
[6]Patent: WO2008/62182,2008,A1 .Location in patent: Page/Page column 110-111
[7]Collection of Czechoslovak Chemical Communications,1932,vol. 4,p. 259,263

3
[ 5382-77-4 ]
[ 98337-06-5 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide

Reference： [1]Stanfield; Daugherty [Journal of the American Chemical Society, 1959, vol. 81, p. 5167,5169]

4
[ 5382-77-4 ]
[ 108630-68-8 ]

Yield	Reaction Conditions	Operation in experiment
	With ethanol; sodium ethanolate
	With water; sodium hydroxide In ethanol at 20℃; for 18h;	1 Step 1: 4- (ethoxycarbonyl) tetrahydro-2H-pyran-4-carboxylic acid To a solution of diethyl dihydro-2H-pyran-4, 4 (3H) -dicarboxylate (900 mg, 3.9 mmol) in EtOH (30 mL) was added NaOH aqueous (3.9 mL, 1mol/L) . The reaction was stirred at 20 for 18 hours, then it was concentrated in vacuum. The residue was diluted in water and acidified to pH 6. The mixture was extracted with EtOAc (40 mL) . The organic layer was washed with brine (20 mL×2) , dried over with Na2SO4, concentrated under vacuum to give the title compound, which was used directly for the next step.
	With water; sodium hydroxide In ethanol at 20℃; for 18h;	Step 1: 4-(ethoxycarbonyl)tetrahydro-2H-pyran-4-carboxylic acid To a solution of diethyl dihydro-2H-pyran-4, 4 (3H) -dicarboxylate (900 mg, 3.9 mmol) in EtOH (30 mL) was added NaOH aqueous (3.9 mL, 1mol/L) . The reaction was stirred at 20 for 18 hours, then it was concentrated in vacuum. The residue was diluted in water and acidified to pH 6. The mixture was extracted with EtOAc (40 mL) . The organic layer was washed with brine (20 mL×2) , dried over with Na2SO4, concentrated under vacuum to give the title compound, which was used directly for the next step.

Reference： [1]Stanfield; Daugherty [Journal of the American Chemical Society, 1959, vol. 81, p. 5167,5169]
[2]Current Patent Assignee: MERCK & CO INC - WO2016/106623, 2016, A1 Location in patent: Page/Page column 142
[3]Current Patent Assignee: MERCK & CO INC - WO2016/106624, 2016, A1 Location in patent: Page/Page column 54

5
[ 111-44-4 ]
[ 105-53-3 ]
[ 5382-77-4 ]

Yield	Reaction Conditions	Operation in experiment
89.1%	With copper(l) iodide; sodium tert-pentoxide In N,N-dimethyl-formamide at 100℃; for 2h; Inert atmosphere;	1 Example 1 Preparation of diethyl 4,4-pyran dicarboxylate (sodium tert-amylate as base) To a nitrogen-protected 1 L three-necked flask, 48.0 g (0.3 mol) of diethyl malonate was added,42.6 g (0.3 mol) of dichloroethyl ether, 480 g of dry DMF and 0.6 g of cuprous iodide to obtain a pale yellow transparent solution. The temperature was raised to 100 ° C with stirring.A solution of sodium tert-amylate in DMF (prepared from 69.3 g of sodium tert-amylate and 277.2 g of DMF) was added dropwise.Reflux 2h,GC tracking to the absence of raw materials remaining, vacuum distillation of solvent, and then continue distillation under reduced pressure, 61.5 g of colorless liquid,Yield: 89.1%.
66%	With sodium ethanolate
52%	With sodium hydride In N,N-dimethyl-formamide at 100℃; for 72h;

48%	With sodium In ethanol	2 Diethyl oxane-4,4-dicarboxylate Diethyl oxane-4,4-dicarboxylate Sodium (20.7 g, 900 mmol) was carefully dissolved in dry ethanol (300 mL) and to this mixture was added diethyl malonate (144 g, 900 mmol) and 2, bis-(2-chloroethyl)ether (129 g, 900 mmol). The reaction mixture was refluxed for 15 h and cooled to room temperature. The solvent was removed by rotary evaporation, the product acidified with 10% HCl (200 mL), extracted with ethyl acetate (4*200 mL) and dried (Na2SO4). Removal of solvent by rotary evaporation, followed by distillation (170-175° C., 22 mm Hg) furnished the product (98.0 g, 48% yield).
44%	Stage #1: diethyl malonate With ethanol; sodium at 20℃; for 0.166667h; Stage #2: 3-oxa-1,5-dichloropentane In ethanol Reflux; Stage #3: With ethanol; sodium at 10℃; Reflux;	2 Reference Example 2; Tetrahydro-pyran-4,4-dicarboxylic acid diethyl ester; A solution of diethyl malonate (15.2 mL, 99.8 mmol) in ethanol (10 mL) was added dropwise to a solution of sodium ethoxide in ethanol [freshly prepared from sodium (2.3 g, 100 mmol) and ethanol (30 mL)] at ambient temperature and stirred for 10 min. Bis(2-chloroethyl)ether (12 mL, 102 mmol) was added dropwise then the mixture was heated at reflux overnight. It was then cooled to 10° C. before another portion of freshly-prepared sodium ethoxide in ethanol [prepared from sodium (2.3 g, 100 mmol) and ethanol (30 mL)] was added. The mixture was heated at reflux for 48 h then cooled, filtered to remove the precipitated sodium chloride then the filtrate was concentrated to dryness. Water was added to the residue which was then extracted with ether (3×25 mL). The combined ether layers were washed with water, brine and dried over anhydrous sodium sulfate. Concentration under reduced pressure yielded tetrahydropyran-4,4-dicarboxylic acid diethyl ester (10.1 g, 44%) as a mobile oil.
44%	Stage #1: diethyl malonate With sodium ethanolate In ethanol at 20℃; for 0.166667h; Stage #2: 3-oxa-1,5-dichloropentane In ethanol Heating / reflux; Stage #3: With sodium ethanolate In ethanol for 48h; Heating / reflux;	3 Reference Example 3; Tetrahydro-pyran-4.,4-dicarboxylic acid diethyl este. rA solution of diethyl malonate (15.2 mL, 99.8 mmol) in ethanol (10 mL) was added dropwise to a solution of sodium ethoxide in ethanol [freshly prepared from sodium (2.3 g, 100 mmol) and ethanol (30 mL)] at ambient temperature and stirred for20 10 min. Bis(2-chloroethyl)ether (12 mL, 102 mmol) was added dropwise and the whole mixture heated at reflux overnight. It was then cooled to 10 0C before another portion of freshly-prepared sodium ethoxide in ethanol [prepared from sodium (2.3g, 100 mmol) and ethanol (30 mL)] was added. The mixture was heated at reflux for 48 h then cooled, filtered to remove the precipitated sodium chloride then the filtrate was concentrated to25 dryness. Water was added to the residue which was then extracted with ether (3 x 25 mL). The combined ether layers were washed with water, brine and dried over anhydrous sodium sulfate. Concentration under reduced pressure yielded tetrahydropyran-4,4-dicarboxylic acid diethyl ester (10.1 g, 44%) as a mobile oil.
	With sodium ethanolate Erhitzen des Reaktionsgemisches mit Natriumaethylat-Loesung;
	With sodium ethanolate 1) ethanol, rt, 2) reflux, 24 h; Yield given. Multistep reaction;
	With sodium In ethanol; ethyl acetate; Petroleum ether	12.i (i) (i) 4,4-Bis(ethoxycarbonyl)tetrahydropyran Sodium (10 g) was dissolved in dry ethanol (300 cm3) and then diethyl malonate (30 g) was added slowly. After stirring for 15 minutes, bis(2-chloroethyl)ether (35 g) was added dropwise. The mixture was heated under reflux for 72 hours and then cooled to room temperature. After filtering the solvent was removed from the reaction mixture under reduced pressure to give the crude product. An initial purification was achieved by chromatography on alumina (activity 4) using ethyl acetate/petroleum ether mixtures as eluants. The pure product (11.3 g) was isolated by distillation under reduced pressure as an oil (b.p. 106°-108° C. at 0.03 mmHg). δ13 C (CDCl3) 13.8(x2), 30.8(x2), 52.1, 61.3(x2), 64.5(x2), 170.6(x2).
	With sodium In ethanol; ethyl acetate; Petroleum ether	12.1 1. 1. 4,4-Bis(ethoxycarbonyl)tetrahydropyran Sodium (10 g) was dissolved in dry ethanol (300 cm3) and then diethyl malonate (30 g) was added slowly. After stirring for 15 minutes, bis(2-chloroethyl)ether (35 g) was added dropwise. The mixture was heated under reflux for 72 hours and then cooled to room temperature. After filtering the solvent was removed from the reaction mixture under reduced pressure to give the crude product. An initial purification was achieved by chromatography on alumina (activity 4) using ethyl acetate/petroleum ether mixtures as eluants. The pure product (11.3 g) was isolated by distillation under reduced pressure as an oil (b.p. 106-108°C at 0.03 mmHg).

Reference： [1]Current Patent Assignee: VALIANT CO., LTD. - CN104910116, 2017, B Location in patent: Paragraph 0019-0030
[2]Current Patent Assignee: ROCHE HOLDING AG - US6342639, 2002, B1 Location in patent: Scheme D
[3]Straessler, Christoph; Linden, Anthony; Heimgartner, Heinz [Helvetica Chimica Acta, 1997, vol. 80, # 5, p. 1528 - 1551]
[4]Current Patent Assignee: CATALYST BIOSCIENCES, INC. - US2004/220214, 2004, A1
[5]Current Patent Assignee: F2G BRITISH BODY CORPORATE - US2011/9390, 2011, A1 Location in patent: Page/Page column 14
[6]Current Patent Assignee: F2G BRITISH BODY CORPORATE; F2G LTD - WO2008/62182, 2008, A1 Location in patent: Page/Page column 110
[7]Kamm; Waldo [Journal of the American Chemical Society, 1921, vol. 43, p. 2225]
[8]Mori, Mitsuo; Takeuchi, Hiroyuki; Minato, Hiroshi; Kobayashi, Michio; Yoshida, Masato; et al. [Phosphorus, Sulfur and Silicon and the Related Elements, 1990, vol. 47, # 1 + 2, p. 157 - 164]
[9]Current Patent Assignee: GENERAL ELECTRIC CO - US4916214, 1990, A
[10]Current Patent Assignee: GENERAL ELECTRIC CO - EP311352, 1991, B1

6
[ 34270-90-1 ]
[ 105-53-3 ]
[ 5382-77-4 ]

Reference： [1]Chemische Berichte,1917,vol. 50,p. 1658

Yield	Reaction Conditions	Operation in experiment
	Red. mit LiAlH4/sd. THF (2 h weiterkochen) --> 4.4-Bis-hydroxymethyl-tetrahydropyran;

Yield	Reaction Conditions	Operation in experiment
	at 100 - 105℃; unter Druck;

10
[ 5382-77-4 ]
[ 5337-03-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 72 percent / 30percent aq. NaOH / 72 h / Ambient temperature 2: 85 percent / 2 h / 180 °C
	Multi-step reaction with 2 steps 1: 88 percent / 10percent aq. HCl / Heating 2: 75 percent / 171 °C
	Multi-step reaction with 2 steps 1: potassium hydroxide; water / ethanol / Heating / reflux 2: 0.5 h / 178 - 180 °C

Reference： [1]Straessler, Christoph; Linden, Anthony; Heimgartner, Heinz [Helvetica Chimica Acta, 1997, vol. 80, # 5, p. 1528 - 1551]
[2]Mori, Mitsuo; Takeuchi, Hiroyuki; Minato, Hiroshi; Kobayashi, Michio; Yoshida, Masato; et al. [Phosphorus, Sulfur and Silicon and the Related Elements, 1990, vol. 47, # 1 + 2, p. 157 - 164]
[3]Current Patent Assignee: F2G BRITISH BODY CORPORATE; F2G LTD - WO2008/62182, 2008, A1

11
[ 5382-77-4 ]
[ 40191-32-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 72 percent / 30percent aq. NaOH / 72 h / Ambient temperature 2: 85 percent / 2 h / 180 °C 3: 91 percent / SOCl₂ / 45 h / Heating