Home Cart 0 Sign in  

[ CAS No. 168828-82-8 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 168828-82-8
Chemical Structure| 168828-82-8
Structure of 168828-82-8 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 168828-82-8 ]

Related Doc. of [ 168828-82-8 ]

Alternatived Products of [ 168828-82-8 ]

Product Details of [ 168828-82-8 ]

CAS No. :168828-82-8 MDL No. :MFCD06658241
Formula : C14H17FN2O4 Boiling Point : -
Linear Structure Formula :- InChI Key :OLDRPBWULXUVTL-LLVKDONJSA-N
M.W : 296.29 Pubchem ID :10541953
Synonyms :

Calculated chemistry of [ 168828-82-8 ]

Physicochemical Properties

Num. heavy atoms : 21
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.5
Num. rotatable bonds : 3
Num. H-bond acceptors : 5.0
Num. H-bond donors : 1.0
Molar Refractivity : 79.6
TPSA : 62.24 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.62 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.02
Log Po/w (XLOGP3) : 0.69
Log Po/w (WLOGP) : 0.64
Log Po/w (MLOGP) : 0.97
Log Po/w (SILICOS-IT) : 1.15
Consensus Log Po/w : 1.09

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.13
Solubility : 2.22 mg/ml ; 0.0075 mol/l
Class : Soluble
Log S (Ali) : -1.57
Solubility : 7.9 mg/ml ; 0.0267 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.25
Solubility : 1.67 mg/ml ; 0.00564 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 1.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 3.09

Safety of [ 168828-82-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 168828-82-8 ]

* 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 [ 168828-82-8 ]
  • Downstream synthetic route of [ 168828-82-8 ]

[ 168828-82-8 ] Synthesis Path-Upstream   1~18

  • 1
  • [ 60456-26-0 ]
  • [ 168828-81-7 ]
  • [ 168828-82-8 ]
YieldReaction ConditionsOperation in experiment
85%
Stage #1: With n-butyllithium; butan-1-ol In tetrahydrofuran; hexane at -15 - 30℃; Inert atmosphere
Stage #2: at -10 - 15℃;
Stage #3: With water In tetrahydrofuran; hexane; ethyl acetate
Example 3: Preparation of(R)-[N-3-(3-Fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl] methanol.[131] Take n-Butanol (51.5g) and THF (100ml) at 20-30°C under Nitrogen atmosphere.After cooling the mix add slowly n- Butyl lithium (1.6M in hexane) (391.7g) at 10 to 20°C maintain it for 45-60 minutes. Take THF (500ml) and N-Car- bobenzoxy-3-fluoro-4-morpholinylaniline (lOOg) at 20-30°C under Nitrogen atmosphere. Cool the mix at -15 to -5°C under stirring. To this solution add slowly n- Butyl lithium solution maintain for 45-60 minutes at -15 to -5°C, to this solution add slowly (R)-(-) Glycidyl butyrate (48.0g) maintain for 1 hour at -10 to -5°C. After completing addition raise the temperature to 8-13°C and maintain for 1 hour then take it to 13-15°C and maintain for 4-5 hours. Organic layer was separated by water (800ml) and Ethyl acetate (300ml). Filter wash the solid with mix of Ethyl acetate- n-Hexane dried in air tray dryer at 55-60°C. Yield: 0.765.: Percentage 85percentw/w.[132]
80%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; Inert atmosphere
Stage #2: at -78 - 20℃;
To a solution of N-(3-Fluoro-4-morpholin-4-ylphenyl)carbamic acid benzyl ester (200 g, 0.606 mol) in THF (1600 mL) under nitrogen at -78°C was added n-butyllithium (416.7 mL, 1.6 M in hexane, 0.666 mol, 1.1 mol eq) over 1.5 h. The reaction mixture was stirred at - 78°C for 2 h, then a solution of R-(-)-glycidyl butyrate (104.7 g, 0.727 mol, 1.2 mol eq) in THF (200 mL) was added at -78°C over 1 h. After stirring at -78°C for 2 h, the reaction mass was warmed to room temperature and stirred for overnight. To the resulting thick slurry is then added saturated ammonium chloride (690 mL) followed by water (100 mL). After stirring at room temperature for 10 min THF layer was separated, aqueous layer was extracted with ethyl acetate (2 x 500 mL). The combined ethyl acetate layer was concentrated under vacuum at 50-55°C to get a residue in which THF layer was added and concentrated completely under vacuum at 50-55°C. Thus obtained solid mass was cooled to room temperature and ethyl acetate (1600 mL) was added. The mixture was heated to 55-60°C and kept stirring for 30 min. The mixture was cooled to 40-42°C, filtered over hyflo and then washed the bed with ethyl acetate (200 mL). The moisture content in the combined ethyl acetate layer was adjusted to 0.29percent by adding demineralised water and then cooled to 30°C. n-Hexane (1200 mL) was charged to the above ethyl acetate solution at 25-30°C and stirred for 12 hr, filtered the solid, washed with a mixture (1 : 1) of ethyl acetate and n-hexane (2 x 200 mL) and dried under vacuum at 50-55°C for 16 hr. The mother liquor was concentrated to dryness under vacuum at 50°C and crystallized from a mixture of ethyl acetate (600 mL) and cyclohexane (600 mL) to get the 2nd crop of (R)-[N-3-(3-fluoro-4-morpholinylphenyl)-2- oxo-5-oxazolidinyl]methanol which matches with the 1 st crop in all respect to provide 142 g material with a combined 80percent yield. Percentage Yield: 80percent
80%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 3.5 h; Inert atmosphere
Stage #2: at -78 - 20℃; Inert atmosphere
[0131] To a solution of N-(3-Fluoro-4-morpholin-4-ylphenyl)carbamic acid benzyl ester (200 g, 0.606 mol) in THF (1600 mL) under nitrogen at −78° C. was added n-butyllithium (416.7 mL, 1.6 M in hexane, 0.666 mol, 1.1 mol eq) over 1.5 h. The reaction mixture was stirred at −78° C. for 2 h, then a solution of R-(−)-glycidyl butyrate (104.7 g, 0.727 mol, 1.2 mol eq) in THF (200 mL) was added at −78° C. over 1 h. After stirring at −78° C. for 2 h, the reaction mass was warmed to room temperature and stirred for overnight. To the resulting thick slurry is then added saturated ammonium chloride (690 mL) followed by water (100 mL). After stirring at room temperature for 10 min THF layer was separated, aqueous layer was extracted with ethyl acetate (2×500 mL). The combined ethyl acetate layer was concentrated under vacuum at 50-55° C. to get a residue in which THF layer was added and concentrated completely under vacuum at 50-55° C. Thus obtained solid mass was cooled to room temperature and ethyl acetate (1600 mL) was added. The mixture was heated to 55-60° C. and kept stirring for 30 min. The mixture was cooled to 40-42° C., filtered over hyflo and then washed the bed with ethyl acetate (200 mL). The moisture content in the combined ethyl acetate layer was adjusted to 0.29percent by adding demineralised water and then cooled to 30° C. n-Hexane (1200 mL) was charged to the above ethyl acetate solution at 25-30° C. and stirred for 12 hr, filtered the solid, washed with a mixture (1:1) of ethyl acetate and n-hexane (2×200 mL) and dried under vacuum at 50-55° C. for 16 hr. The mother liquor was concentrated to dryness under vacuum at 50° C. and crystallized from a mixture of ethyl acetate (600 mL) and cyclohexane (600 mL) to get the 2nd crop of (R)—[N-3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl]methanol which matches with the 1st crop in all respect to provide 142 g material with a combined 80percent yield. [0132] Percentage Yield: 80percent
77.7%
Stage #1: With n-butyllithium In tetrahydrofuran at -85 - -75℃; for 2 h;
Stage #2: Heating
A solution of N-benzyloxycarbonyl-3-fluoro-4-morpholinoaniline (2.0 g, 6.06 mmol) and tetrahydrofuran, Cooled to -85 to -75 ° C, a solution of n-butyllithium (2.80 mL, 7.03 mmol)The reaction was continued for 2 hours.A solution of (R) -butyric acid glycidyl ester (0.90 g, 6.06 mmol) in tetrahydrofuran was then added dropwise and the temperature was naturally warmed to the reaction overnight.TLC monitoring, the reaction is completed.To the reaction was added 30 mL of saturated NH4Cl solution and dichloromethane, stirred for 2 minutes,The phases were separated and the aqueous phase was extracted with CH2Cl2. The organic phases were combined, washed with water, saturated NaCl solution,Dried over anhydrous Na2SO4 and concentrated to give the crude product.Recrystallization to give the product as a lavender powder(R) - [3- (3-fluoro-4-morpholinophenyl) -2-oxo-5-oxazolidinyl] methyl alcohol, 1.39 g,Yield: 77.7percent, chemical purity: 99.3percent; optical purity: 98.68percent.
70%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 3.5 h; Inert atmosphere
Stage #2: at -78 - 20℃;
Stage #3: With ammonium chloride In tetrahydrofuran; hexane; water at 20℃; for 0.166667 h;
Example-6(b): Preparation of (R)-[N-3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5- oxazolidinyl] methanol (VIII) starting from N-carbobenzoxy-3-fluoro-4- morpholinylanilineN-carbobenzoxy-3-fluoro-4-morpholinylaniline (100 g) was dissolved in THF (800 ml). To the resulting solution, n-butyllithium (208 ml in hexane) was added under nitrogen at -78°C over 1.5h and stirred for 2h, further a solution of R-(-)-glycidyl butyrate (52.3 g in THF (100 ml)) was added and stirred for 2h. The reaction mixture was warmed to room temperature and stirred for overnight. To the resulting thick slurry saturated ammonium chloride (345 ml) was added followed by the addition of water (50 ml). It was stirred at room temperature for 10 min and THF layer was separated from aqueous layer. Aqueous layer was extracted with ethyl acetate (2 x 250 ml). The combined ethyl acetate layer was washed with water and concentrated to get a residue in which THF layer was added and further concentrated completely. The solid mass obtained was cooled to room temperature and ethyl acetate (600 ml) was added. The reaction mixture was heated to 60-65°C and was stirred for 30 min, which was further cooled to 40-45 °C. The cooled reaction mixture was filtered and was washed with ethyl acetate (100 ml). To the filtrate cyclohexane (450 ml) was added at 25-35°C in 5 min. The resulting mixture was stirred for 12h. The precipitated solid was filtered, washed with a mixture (1 :1) of ethyl acetate and cyclohexane and dried to obtain the titled compound (62 g) with 70percent yield.
64%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5 h;
Stage #2: at -78 - 20℃;
Stage #3: With ammonium chloride In tetrahydrofuran; hexane; water
To a solution of 390 g of N-carbobenzyloxy-3-fluoro-4-morpholinyl aniline in 5.50 L of tetrahydrofuran at -78°C under nitrogen was added 770ml of 1.6M n-butyl lithium/hexane over 30 min. Further 183.2 g of (R)-glycidyl butyrate in 300 ml of tetrahydrofuran was added to the obtained reaction mixture over 30 min followed by stirring for 1 hr at -78°C. After the completion of reaction, the reaction mass was allowed to come to ambient temperature gradually. After stirring the mixture overnight, 200 ml of saturated aqueous ammonium chloride was added, followed by 5 L of water. The aqueous layer was extracted with ethyl acetate (4 x 3.0 L) and the combined organic layer was concentrated to get a light purple solid. Yield: 249.6 g.; Percentage: 64percent w/w
78 g
Stage #1: With n-butyllithium In tetrahydrofuran at -30 - -20℃;
Stage #2: at -30 - 50℃;
II.
Preparation of (R)-N-[[3-(3-fluoro-4-morpholinyl)phenyl]-2-oxo-5- oxazolidinyl] methanol
N-carbobenzyloxy-3-fluoro-4-morpholinyl aniline (100 g) and tetrahydrofuran (1100.0 ml) at 25-30°C in RBF and cooled to -20°C to -30°C. n-BuLi (250.0ml) was added slowly for a period of 30-40 minutes to the reaction mixture at -20 °C to -30 °C and stirred for 35- 40 minutes. A solution of R-glycidyl butyrate (46. Ogm) in THF (50.0ml) was added to reaction mass at -20 °C to -30 °C within 20 to 30 minutes and maintained for 1 hour at -20 °C to -30 °C. The temperature of the reaction mass was slowly raised to 45-50°C within 40-60 minutes, maintained for 2 hours at 45-50 °C and then cooled to 25-30°C. The reaction mass was quenched with aqueous NH4C1 solution (5percent) (400.0ml) at 25-30°C and then toluene (400.0 ml) was charged at 25-30°C. Two layers were separated and the obtained organic layer was concentrated under vacuum at 40-45°C to get thick slurry. Toluene (300ml) was added to the residue at 25-30°C, stirred for 30 minutes at 25-30°C, cooled to 5-10°C and stirred for lhour. The suspension was filtered, washed the solid with toluene (2x100.0 ml) and dried in air oven for 30 mins at 25-30°C followed by at 40-45°C to obtain titled compound.Dry weight: 78gm

Reference: [1] Synthetic Communications, 2010, vol. 40, # 6, p. 789 - 798
[2] Patent: WO2011/77310, 2011, A1, . Location in patent: Page/Page column 12
[3] Organic Syntheses, 2005, vol. 81, p. 112 - 120
[4] Patent: WO2013/111048, 2013, A1, . Location in patent: Page/Page column 19; 20
[5] Patent: US2015/25236, 2015, A1, . Location in patent: Paragraph 0131; 0132
[6] Patent: CN102617500, 2016, B, . Location in patent: Paragraph 0042; 0043
[7] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 3, p. 1302 - 1305
[8] Patent: WO2011/114210, 2011, A2, . Location in patent: Page/Page column 22
[9] Patent: WO2009/63505, 2009, A2, . Location in patent: Page/Page column 14
[10] J. Med. Chem., 1996, vol. 39, # 3, p. 673 - 679
[11] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 6, p. 857 - 859
[12] Organic and Biomolecular Chemistry, 2008, vol. 6, # 24, p. 4634 - 4642
[13] Patent: WO2013/72923, 2013, A1, . Location in patent: Page/Page column 16-17
[14] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 779 - 785
[15] Patent: WO2015/68121, 2015, A1, . Location in patent: Page/Page column 14
[16] European Journal of Medicinal Chemistry, 2015, vol. 106, p. 120 - 131
  • 2
  • [ 124-38-9 ]
  • [ 168828-82-8 ]
Reference: [1] Organic Letters, 2018, vol. 20, # 16, p. 5036 - 5039
  • 3
  • [ 496031-56-2 ]
  • [ 168828-82-8 ]
YieldReaction ConditionsOperation in experiment
50 g With water; sodium t-butanolate In tetrahydrofuran at 0 - 15℃; for 0.5 h; (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl acetate (62 gr) is mixed with tetrahydrofuran (300 ml), cooled to 0-5° C.
Slowly added sodium tert-butoxide (17.5 gr) at 0-5° C. and followed by slow addition of DM water (620 ml) at 10-15° C.
The reaction mass is stirred for 30 min at 10-15° C., After completion of the reaction, methylene dichloride is added (300 ml), further extracted with methylene dichloride (120 ml).
Solvent is evaporated completely U/vaccum.
The precipitated solid is crystallized from hexane (150 ml).
Isolated solid is filtered and washed with hexane.
Dried the material at 50-55° C. to give 50 gr of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol.
Reference: [1] Patent: WO2012/114355, 2012, A1, . Location in patent: Page/Page column 11
[2] Patent: US2013/324719, 2013, A1, . Location in patent: Paragraph 0022; 0054-0055
  • 4
  • [ 369-34-6 ]
  • [ 168828-82-8 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 6, p. 857 - 859
[2] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 4, p. 353 - 360
[3] J. Med. Chem., 1996, vol. 39, # 3, p. 673 - 679
[4] Patent: WO2011/77310, 2011, A1,
[5] Patent: WO2011/114210, 2011, A2,
[6] Patent: WO2011/114210, 2011, A2,
[7] Patent: WO2012/114355, 2012, A1,
[8] Patent: WO2013/72923, 2013, A1,
[9] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 779 - 785
[10] Patent: US2013/324719, 2013, A1,
[11] European Journal of Organic Chemistry, 2014, vol. 2014, # 34, p. 7614 - 7620
[12] Patent: WO2015/68121, 2015, A1,
[13] European Journal of Medicinal Chemistry, 2015, vol. 106, p. 120 - 131
[14] Patent: CN102617500, 2016, B,
  • 5
  • [ 2689-39-6 ]
  • [ 168828-82-8 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 6, p. 857 - 859
[2] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 4, p. 353 - 360
[3] J. Med. Chem., 1996, vol. 39, # 3, p. 673 - 679
[4] Patent: WO2011/77310, 2011, A1,
[5] Patent: WO2011/114210, 2011, A2,
[6] Patent: WO2011/114210, 2011, A2,
[7] Patent: WO2012/114355, 2012, A1,
[8] Patent: WO2013/72923, 2013, A1,
[9] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 779 - 785
[10] Patent: US2013/324719, 2013, A1,
[11] European Journal of Organic Chemistry, 2014, vol. 2014, # 34, p. 7614 - 7620
[12] European Journal of Medicinal Chemistry, 2015, vol. 106, p. 120 - 131
[13] Patent: CN102617500, 2016, B,
  • 6
  • [ 565176-83-2 ]
  • [ 60456-26-0 ]
  • [ 168828-82-8 ]
YieldReaction ConditionsOperation in experiment
80%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 3.5 h; Inert atmosphere
Stage #2: at -78 - 20℃;
Stage #3: With ammonium chloride In tetrahydrofuran; hexane; water at 20℃; for 0.5 h;
Example-S(a): Preparation of (R)-[N-3-(3-fluoro-4-morpholinylphenyl)-2- oxo-5- oxazolidinyljmethanol (VIII) starting from N-carboethoxy-3-fluoro-4- morpholinylanilineN-carboethoxy-3-fluoro-4-morpholinylaniline (100 g) was dissolved in THF (500 ml). To the resulting solution, n-butyllithium (245 ml in hexane) was added under nitrogen at -78°C over 1.5h and stirred for 2h, further a solution of R-(-)-glycidyl butyrate (53.75 g, in THF (100 ml)) was added. The resulting solution was stirred at -78°C for 2h, further it was warmed to room temperature and stirred for overnight. To the resulting thick slurry, saturated ammonium chloride (345 ml) was added followed by the addition of water (300 ml). It was stirred at room temperature for 30 min and was concentrated. Further, water (500 ml) was added and the suspension was again stirred at 50-55°C for lh and then at 25-30°C for next lh. The solid mass was filtered, washed with water and suck dried for lh. The filtrate was extracted with toluene. To the combined toluene layer, the suck dried material obtained above was added and heated to reflux and further concentrated. The concentrated solution was cooled to room temperature and stirred for lh. The solid mass was filtered, washed with toluene and dried to obtain the titled compound (110 g) with 80percent yield.
Reference: [1] Patent: WO2011/114210, 2011, A2, . Location in patent: Page/Page column 20
  • 7
  • [ 912552-56-8 ]
  • [ 168828-82-8 ]
Reference: [1] Tetrahedron Letters, 2006, vol. 47, # 38, p. 6799 - 6802
  • 8
  • [ 93246-53-8 ]
  • [ 168828-82-8 ]
Reference: [1] Tetrahedron Letters, 2006, vol. 47, # 38, p. 6799 - 6802
[2] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 6, p. 857 - 859
[3] J. Med. Chem., 1996, vol. 39, # 3, p. 673 - 679
[4] Patent: WO2011/77310, 2011, A1,
[5] Patent: WO2011/114210, 2011, A2,
[6] Patent: WO2011/114210, 2011, A2,
[7] Patent: WO2012/114355, 2012, A1,
[8] Patent: WO2013/72923, 2013, A1,
[9] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 779 - 785
[10] Patent: US2013/324719, 2013, A1,
[11] European Journal of Organic Chemistry, 2014, vol. 2014, # 34, p. 7614 - 7620
[12] European Journal of Medicinal Chemistry, 2015, vol. 106, p. 120 - 131
[13] Patent: CN102617500, 2016, B,
[14] Organic Letters, 2018, vol. 20, # 16, p. 5036 - 5039
  • 9
  • [ 903593-93-1 ]
  • [ 32315-10-9 ]
  • [ 168828-82-8 ]
Reference: [1] Heteroatom Chemistry, 2008, vol. 19, # 3, p. 316 - 319
  • 10
  • [ 912552-55-7 ]
  • [ 168828-82-8 ]
Reference: [1] Tetrahedron Letters, 2006, vol. 47, # 38, p. 6799 - 6802
  • 11
  • [ 912552-54-6 ]
  • [ 168828-82-8 ]
Reference: [1] Tetrahedron Letters, 2006, vol. 47, # 38, p. 6799 - 6802
  • 12
  • [ 905945-96-2 ]
  • [ 168828-82-8 ]
Reference: [1] Tetrahedron Letters, 1999, vol. 40, # 26, p. 4855 - 4856
  • 13
  • [ 239438-43-8 ]
  • [ 168828-82-8 ]
Reference: [1] Tetrahedron Letters, 1999, vol. 40, # 26, p. 4855 - 4856
  • 14
  • [ 239438-39-2 ]
  • [ 168828-82-8 ]
Reference: [1] Tetrahedron Letters, 1999, vol. 40, # 26, p. 4855 - 4856
  • 15
  • [ 868405-66-7 ]
  • [ 168828-82-8 ]
Reference: [1] Patent: WO2012/114355, 2012, A1,
[2] Patent: US2013/324719, 2013, A1,
  • 16
  • [ 60827-45-4 ]
  • [ 168828-81-7 ]
  • [ 168828-82-8 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 34, p. 7614 - 7620
  • 17
  • [ 60456-26-0 ]
  • [ 93246-53-8 ]
  • [ 168828-82-8 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 4, p. 353 - 360
  • 18
  • [ 124-63-0 ]
  • [ 168828-82-8 ]
  • [ 174649-09-3 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine In dichloromethane at 0℃; for 0.5 h; To a solution of 132.8 g of (R)-N-[[3-[3-fluoro-4-morpholinyl]phenyl]-2-oxo-5- oxazolidinyl] methanol and 87.1 g of triethylamine in IL of methylene dichloride at O0C under nitrogen was added 74 gm of methanesulfonyl chloride. The reaction mixture was allowed to stir at 0°C for 30 min, then allowed to warm to ambient temperature. A white solid was precipitated. 1.75 L water, 6.50 L methylene dichloride and IL ethyl acetate mixture were added followed by stirring for 30 min. The reaction mass was filtered to get a white solid. Yield: 140 g.; Percentage: 105.42percent w/w
96% With triethylamine In tetrahydrofuran at 8 - 15℃; for 3.75 h; Cooling with ice; Inert atmosphere Example 1
Preparation of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxazolidin-5-yl)methyl methanesulfonate (compound (V) with R2 = methyl)
To a solution of ((R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl)methanol (20 g, 67.5 mmol) in tetrahydrofuran (220 mL, 11 mL/g) at room temperature under inert atmosphere was added triethylamine (12.2 mL, 87.8 mmol, 1.3 eq).
The mixture was cooled in an ice bath and methanesulfonyl chloride (6.8 mL, 87.8 mmol, 1.3 eq) was added dropwise over approximately 15 min (resulting in an increase in Tint from 8 to 15 °C.
A pale lilac precipitate forms immediately).
The ice bath is removed and the suspension is stirred for 3.5 h.
The suspension was filtered at room temperature and the solids (32.9 g) were suspended in water (165 mL, 5 vol) and stirred for 2 h at room temperature.
The suspension was filtered and a second suspension in water was carried out (as above).
The suspension was filtered and the collected solids were dried in-vacuo (60 °C, 2-4 mm Hg) to give ((R)-3-(3-fluoro-4-morpholinophenyl)-2-oxazolidin-5-yl)methyl methanesulfonate (24.4 g, 96percent) as a pale lilac powder.
1H NMR (400 MHz, acetone-d6): δ 7.57 (dd, 1H, ArH, J 2.8 and 15 Hz), 7.23 (ddd, 1H, ArH, J 2.7 and 9 Hz), 7.07 (t, 1H, ArH, J 9Hz), 5.05-5.01 (m, 1H, CH), 4.58 (qd, 2H, CH2, J 3, 5, 8.5 and 12 Hz), 4.30 (t, 1H, CH, J 9 Hz), 3.99 (dd, 1H, CH, J 6 and 9 Hz), 3.79-3.77 (m, 4H, CH2), 3.20 (s, 3H, CH3), 3.03-3.01 (m, 4H, CH2) ppm.
Mp 178.7 - 180.6 °C
[α]D-55.5° (c 0.98, acetone)
95% With triethylamine In dichloromethane at 20 - 30℃; (R)-[N-3-(3-Fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl] methyl methane sulfonate[134] Triethyl amine (68.2g), Methane sulfonyl chloride (48.3g) are added to a flaskcontaining Dichloromethane (1900ml) and(R)-[N-3-(3-Fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl] methanol (lOOg) at 20-30°C with constant stirring for 2-3 hours. After cooling filtration wash the solid with Dichloromethane followed by water wash dried in air tray dryer. Yield: 1.20.: Percentage 95 w/w.[135]
90% With triethylamine In dichloromethane at 0 - 40℃; Example-1: Preparation of (5R)-(N)-[[3-fluoro-(4-morpholinylphenyl)-2-oxo-5-oxazolidinyl] methyl] sulphonate.(5R)-(N)-[3-fluoro-(4-morpholinylphenyl)-2-oxo-5-oxazolidinyl]methanol (1 mole eq, 100 g) was taken in 600 ml methylene dichloride and cooled to 0-50C, to it was added triethylamine 1.92 mol eq, 90.2 ml). The reaction mixture was stirred to 10-15mins followed by the addition of methanesulfonyl chloride (1.44 mole eq, 37.5ml) at the same temperature. The temperature of the reaction mixture was raised to room temperature and further to 400C with continuous stirring for 7 - 8 hours. The reaction mixture was quenched with water and stirred for lhr at room temperature, filtered, washed with methylene dichloride and dried to obtain the titled compound (Yield : 90percent).
73% With triethylamine In dichloromethane at 0 - 20℃; for 10 h; Example-8: Preparation of (R)-[[N-3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5- oxazolidinyljmethyl] 4-methylmethanesulfonate (IX)(R)-[N-3-(3-fluoro-4-mo holinylphenyl)-2- oxo-5-oxazolidinyl] methanol (6.5 g) and methanesulfonyl chloride (3.78 g) were dissolved in DCM (60 ml). The resulting solution was cooled to 0-5°C and to the cold solution; triethylamine (3.76 g) was added. The obtained solution was warmed to room temperature and stirred for lOh. After the completion of reaction, it was concentrated. In the resulting reaction mass, water (50 ml) was added and stirred at 50-55°C for lh and further at 25-30°C for next lh. The solid obtained was filtered, washed with water and suck dried. The suck dried material was suspended in methanol (65 ml) and heated to 60°C. The suspension was stirred at 55-60°C for 2h and further at room temperature for lh. The solid was filtered, washed with methanol at room temperature and dried to obtain the titled compound (6 g) with 73percent yield.
95 g With triethylamine In dichloromethane at 45℃; ExampIe-3: (R)-fN-f3-(3-fluoro-4-morphoIinylphenylV-2-oxo-5- oxazolidinyll methyl] methane sulfonateTo a solution of 100 g of N-carbobenzyloxy-3-fluoro-4-morpholinyl aniline in 500 mL of freshly distilled tetrahydrofuran at -80°C under nitrogen, was added 105 mL of n-butyl lithium/hexane via syringe within 90 minutes, and the mixture stirred for 60 minutes. Further, a solution of 45.9 g of (R)-glycidylbutyrate in 80 mL of tetrahydrofuran was added within 90 minutes, and stirred for 60 minutes. The reaction mixture was removed from the dry ice bath, and allowed to come to ambient temperature. After stirring for 4-6 hours, the reaction mixture was quenched in 134 g of saturated aqueous ammonium chloride solution, followed by 500 mL of toluene, and the aqueous layer extracted with toluene. The combined organic layers were washed with 360 mL of brine. The organic layer was treated with 4 g activated charcoal and stirred for 30 minute and filtered. The filtrate was concentrated under vacuum at 60°C to remove toluene completely. In the mixture of residue of (R)-N-[[3-[3-fluoro-4- moφholinyl]-phenyl]-2-oxo-5-oxazolidinyl]methanol, 300 mL methylene dichloride and 46 g triethylamine mixture was added within 90 minutes. The reaction mixture was warmed to 45°C and stirred for 3 hours. Methylene dichloride was removed under vacuum below 50°C and the residue was cooled to room temperature. The residue were triturated with 500 mL of toluene and stirred for 1 hour and filtered. The wet-cake was washed with toluene and slurried in water for 1 hour. The solid was filtered and washed with water. The product dried at 60°C to 65°C to get 95 g (84percent) of (R)-[N-[3-(3- fluoro-4-mo holinylphenyl)-2-oxo-5-oxazolidinyl]methyl]methane sulfonate.
40 g With triethylamine In dichloromethane at 0 - 5℃; for 0.5 h; (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol (50 gr) and triethylamine (42.6 gr) in methylene dichloride (250 ml) was cooled in ice-bath and treated with methane sulphonyl chloride (38.2 gr).
The mixture was stirred for 30 min at 0-5° C.
The precipitated product is filtered and washed with chilled DM water (250 ml).
Dried the material at 50-55° C. to give 40 gr of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl methanesulphonate.
122 g With triethylamine In dichloromethane at 0 - 5℃; III.
Preparation of (R)-N-[[3-(3-fluoro-4-morpholinyl)phenyl]-2-oxo-5- oxazolidinyljmethansulfonate:
Dichloromethane (1800.0ml), f )-N-[[3-(3-fluoro-4-moφholinyl)phenyl]-2-oxo-5- oxazolidinyljmethanol (100. Ogm), triethyl amine (68.45gm) were charged into RBF at 25- 30°C and cooled to 0-5°C. A solution of methane sulphonyl chloride (53.78gm) and in MDC (200.0ml) was added slowly for a period of 25-30 minutes to the reaction mass at 0- 5°C and stirred for 2 hours. After reaction completion, the reaction mass was concentrated to thick slurry under vacuum at 35-40°C and then chased with water (200.0 ml) at 35-40°C to remove traces of dichloromethane. Water (800.0ml) was charged to the reaction mass at 35-40°C, cooled to 25-30°C and stirred for 30 minutes. The suspension was filtered, washed the solid with water (2x250.0ml) followed by with methanol (100.0ml) and suck dried. The wet solid was stirred in methanol (200.0 ml) for 30 minutes at 25-30°C, filtered the solid and washed with methanol (2x100.0ml) and then suck dried. The obtained solid was dried in an air oven at 25-30°C for 30 minutes followed by at 45-50°C to afford titled compound

Reference: [1] Patent: WO2009/63505, 2009, A2, . Location in patent: Page/Page column 14
[2] Patent: EP2163547, 2010, A1, . Location in patent: Page/Page column 8
[3] Patent: WO2011/77310, 2011, A1, . Location in patent: Page/Page column 12; 13
[4] Synthetic Communications, 2010, vol. 40, # 6, p. 789 - 798
[5] Patent: WO2010/84514, 2010, A2, . Location in patent: Page/Page column 15
[6] Patent: WO2011/114210, 2011, A2, . Location in patent: Page/Page column 23
[7] J. Med. Chem., 1996, vol. 39, # 3, p. 673 - 679
[8] Tetrahedron Letters, 1999, vol. 40, # 26, p. 4855 - 4856
[9] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 4, p. 353 - 360
[10] Tetrahedron Letters, 2006, vol. 47, # 38, p. 6799 - 6802
[11] European Journal of Medicinal Chemistry, 2009, vol. 44, # 8, p. 3217 - 3227
[12] Organic and Biomolecular Chemistry, 2008, vol. 6, # 24, p. 4634 - 4642
[13] Patent: WO2012/114355, 2012, A1, . Location in patent: Page/Page column 11
[14] Patent: WO2013/72923, 2013, A1, . Location in patent: Page/Page column 16-17
[15] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 779 - 785
[16] Patent: US2013/324719, 2013, A1, . Location in patent: Paragraph 0022; 0056-0057
[17] Patent: WO2015/68121, 2015, A1, . Location in patent: Page/Page column 15
[18] European Journal of Medicinal Chemistry, 2015, vol. 106, p. 120 - 131
Same Skeleton Products
Historical Records

Pharmaceutical Intermediates of
[ 168828-82-8 ]

Linezolid Related Intermediates

Chemical Structure| 168828-90-8

[ 168828-90-8 ]

(S)-5-(Aminomethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Chemical Structure| 369-34-6

[ 369-34-6 ]

3,4-Difluoronitrobenzene

Chemical Structure| 496031-57-3

[ 496031-57-3 ]

(R)-5-(Chloromethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Chemical Structure| 174649-09-3

[ 174649-09-3 ]

(R)-(3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate

Chemical Structure| 93246-53-8

[ 93246-53-8 ]

3-Fluoro-4-morpholinoaniline

Related Functional Groups of
[ 168828-82-8 ]

Fluorinated Building Blocks

Chemical Structure| 168828-90-8

[ 168828-90-8 ]

(S)-5-(Aminomethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.95

Chemical Structure| 149524-42-5

[ 149524-42-5 ]

(R)-3-(3-Fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one

Similarity: 0.93

Chemical Structure| 496031-57-3

[ 496031-57-3 ]

(R)-5-(Chloromethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.87

Chemical Structure| 167010-30-2

[ 167010-30-2 ]

(S)-N-((3-(3,5-Difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Similarity: 0.85

Chemical Structure| 174649-09-3

[ 174649-09-3 ]

(R)-(3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate

Similarity: 0.83

Aryls

Chemical Structure| 168828-90-8

[ 168828-90-8 ]

(S)-5-(Aminomethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.95

Chemical Structure| 149524-42-5

[ 149524-42-5 ]

(R)-3-(3-Fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one

Similarity: 0.93

Chemical Structure| 496031-57-3

[ 496031-57-3 ]

(R)-5-(Chloromethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.87

Chemical Structure| 167010-30-2

[ 167010-30-2 ]

(S)-N-((3-(3,5-Difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Similarity: 0.85

Chemical Structure| 174649-09-3

[ 174649-09-3 ]

(R)-(3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate

Similarity: 0.83

Alcohols

Chemical Structure| 149524-42-5

[ 149524-42-5 ]

(R)-3-(3-Fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one

Similarity: 0.93

Chemical Structure| 444335-16-4

[ 444335-16-4 ]

(R)-3-(4-Bromo-3-fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one

Similarity: 0.82

Chemical Structure| 434958-85-7

[ 434958-85-7 ]

N-Boc-5-Hydroxyindole

Similarity: 0.61

Chemical Structure| 957204-30-7

[ 957204-30-7 ]

tert-Butyl 6-hydroxyindoline-1-carboxylate

Similarity: 0.60

Chemical Structure| 327044-56-4

[ 327044-56-4 ]

tert-Butyl 6-hydroxy-3,4-dihydroquinoline-1(2H)-carboxylate

Similarity: 0.60

Amides

Chemical Structure| 168828-90-8

[ 168828-90-8 ]

(S)-5-(Aminomethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.95

Chemical Structure| 149524-42-5

[ 149524-42-5 ]

(R)-3-(3-Fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one

Similarity: 0.93

Chemical Structure| 496031-57-3

[ 496031-57-3 ]

(R)-5-(Chloromethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.87

Chemical Structure| 167010-30-2

[ 167010-30-2 ]

(S)-N-((3-(3,5-Difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Similarity: 0.85

Chemical Structure| 174649-09-3

[ 174649-09-3 ]

(R)-(3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate

Similarity: 0.83

Related Parent Nucleus of
[ 168828-82-8 ]

Aliphatic Heterocycles

Chemical Structure| 168828-90-8

[ 168828-90-8 ]

(S)-5-(Aminomethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.95

Chemical Structure| 149524-42-5

[ 149524-42-5 ]

(R)-3-(3-Fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one

Similarity: 0.93

Chemical Structure| 496031-57-3

[ 496031-57-3 ]

(R)-5-(Chloromethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.87

Chemical Structure| 167010-30-2

[ 167010-30-2 ]

(S)-N-((3-(3,5-Difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Similarity: 0.85

Chemical Structure| 174649-09-3

[ 174649-09-3 ]

(R)-(3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate

Similarity: 0.83

Morpholines

Chemical Structure| 168828-90-8

[ 168828-90-8 ]

(S)-5-(Aminomethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.95

Chemical Structure| 496031-57-3

[ 496031-57-3 ]

(R)-5-(Chloromethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.87

Chemical Structure| 174649-09-3

[ 174649-09-3 ]

(R)-(3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate

Similarity: 0.83

Chemical Structure| 446292-10-0

[ 446292-10-0 ]

(S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one

Similarity: 0.72

Chemical Structure| 898543-06-1

[ 898543-06-1 ]

(S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one hydrochloride

Similarity: 0.71

Oxazolidines

Chemical Structure| 168828-90-8

[ 168828-90-8 ]

(S)-5-(Aminomethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.95

Chemical Structure| 149524-42-5

[ 149524-42-5 ]

(R)-3-(3-Fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one

Similarity: 0.93

Chemical Structure| 496031-57-3

[ 496031-57-3 ]

(R)-5-(Chloromethyl)-3-(3-fluoro-4-morpholinophenyl)oxazolidin-2-one

Similarity: 0.87

Chemical Structure| 167010-30-2

[ 167010-30-2 ]

(S)-N-((3-(3,5-Difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Similarity: 0.85

Chemical Structure| 174649-09-3

[ 174649-09-3 ]

(R)-(3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl methanesulfonate

Similarity: 0.83