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Chemical Structure| 17016-83-0 Chemical Structure| 17016-83-0

Structure of 17016-83-0

Chemical Structure| 17016-83-0

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Synonyms: (S)-4-Isopropyl-2-oxazolidinone

4.5 *For Research Use Only !

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Product Details of [ 17016-83-0 ]

CAS No. :17016-83-0
Formula : C6H11NO2
M.W : 129.16
SMILES Code : O=C1OC[C@H](C(C)C)N1
Synonyms :
(S)-4-Isopropyl-2-oxazolidinone
MDL No. :MFCD00010847
InChI Key :YBUPWRYTXGAWJX-RXMQYKEDSA-N
Pubchem ID :7157133

Safety of [ 17016-83-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 17016-83-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.83
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 37.23
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

38.33 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.51
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.12
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

0.37
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.41
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.83
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.85

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.28
Solubility 6.77 mg/ml ; 0.0524 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.52
Solubility 3.92 mg/ml ; 0.0303 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.94
Solubility 14.7 mg/ml ; 0.114 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.29 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.22

Application In Synthesis of [ 17016-83-0 ]

* 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.

  • Downstream synthetic route of [ 17016-83-0 ]

[ 17016-83-0 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 124-41-4 ]
  • (S)-3-(4-Dimethylamino-benzoyl)-4-isopropyl-oxazolidin-2-one [ No CAS ]
  • [ 1202-25-1 ]
  • [ 17016-83-0 ]
  • 2
  • [ 169556-48-3 ]
  • [ 17016-83-0 ]
  • 3
  • [ 15893-42-2 ]
  • [ 17016-83-0 ]
  • 4(S)-isopropyl-3-[3-(4-methoxyphenyl)-1-oxobutyl]-2-oxazolidinone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; ammonium chloride; In tetrahydrofuran; hexane; PREPARATION 11 4(S)-Isopropyl-3-[3-(4-methoxyphenyl)-1-oxobutyl]-2-oxazolidinone 18.19 ml (29.1 mmoles) of butyllithium (as a 1.6M hexane solution) were added dropwise at -78 C. and under an atmosphere of nitrogen to a solution of 3.13 g (24.2 mmoles) of 4(S)-isopropyl-2-oxazolidinone in 50 ml of anhydrous tetrahydrofuran, and then the mixture was stirred for 30 minutes. At the end of this time, a solution of 5.43 g (29.1 mmoles) of <strong>[15893-42-2]3-(4-methoxyphenyl)propionyl chloride</strong> in 20 ml of anhydrous tetrahydrofuran was added dropwise to the resulting mixture over the course of 10 minutes. The mixture was then stirred for a further 1 hour, after which a saturated aqueous solution of ammonium chloride was added to the reaction mixture, which was then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by medium pressure silica gel column chromatography (using a 1:3 by volume mixture of ethyl acetate and hexane as eluent), followed by recrystallization from diisopropyl ether, to give 5.63 g (yield 80%) of the title compound as white crystals, melting at 62.0-63.5 C. [α]D20 =+60.4 (C=1, chloroform). Elemental analysis: Calculated for C16 H21 NO4: C, 65.96%; H, 7.27%; N, 4.81%. Found: C, 65.98%; H, 7.25%; N, 4.75%. Mass spectrum (m/e): 291 (M+), 162, 134, 121. Infrared Absorption Spectrum (KBr) νmax cm-1: 1777, 1698.
  • 4
  • [ 17016-83-0 ]
  • [ 928-50-7 ]
  • [ 116386-68-6 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In tetrahydrofuran; hexane; EXAMPLE 12 (S)-4-(1-Methylethyl)-3-(1-Oxo-4-Pentenyl)-2-Oxazolidinone To a -78 C. solution of 5.0 g of 4-(1-methylethyl)-2-oxazolidinone in 80 ml of tetrahydrofuran is added, dropwise, 15.5 ml of 2.5M n-butyl lithium in hexane. After stirring for 30 minutes, a solution of 4.8 g of <strong>[928-50-7]4-pentenyl chloride</strong> in 30 ml of tetrahydrofuran is added, dropwise, and the resulting solution is stirred at -78 C. for 3.5 hours. The reaction is diluted with aqueous ammonium chloride and diethyl ether. The organic layer is washed with water, dried and concentrated in vacuo. The residue is purified by chromatography (silica gel, 25% ethyl acetate/petroleum ether) to give 5.8 g of the desired product as a pale yellow oil. [alpha]D26 =+79 (methylene chloride).
  • 5
  • [ 24424-99-5 ]
  • 6-((S)-4-Isopropyl-2-oxo-oxazolidin-3-yl)-pyridine-2-carbaldehyde [ No CAS ]
  • [ 17016-83-0 ]
  • [ 134441-61-5 ]
  • 6
  • [ 18643-86-2 ]
  • [ 17016-83-0 ]
  • [ 1351791-43-9 ]
  • 7
  • [ 1186202-35-6 ]
  • [ 17016-83-0 ]
  • [ 1401067-00-2 ]
YieldReaction ConditionsOperation in experiment
Preparation 1B (4S)-4-(Propan-2-yl)-3-(5,5,5-trifluoropentanoyl)-1,3-oxazolidin-2-one To a stirred solution of 5,5,5-trifluoropentanoic acid (5.04 g, 32.3 mmol) in DCM (50 mL) and DMF (3 drops) was added oxalyl chloride (3.4 mL, 38.8 mmol) dropwise over 5 min and the solution was stirred until all bubbling subsided. The reaction mixture was concentrated under reduced pressure to give pale yellow oil. To a separate flask charged with a solution of (4S)-4-(propan-2-yl)-1,3-oxazolidin-2-one (4.18 g, 32.4 mmol) in THF (100 mL) at -78 C. was added n-BuLi (2.5M in hexane) (13.0 mL, 32.5 mmol) dropwise via syringe over 5 min. After stirring for 10 min, the above acid chloride dissolved in THF (20 mL) was added via cannula over 15 min. The reaction mixture was warmed to 0 C., and was allowed to warm to room temperature as the bath warmed and stirred overnight. To the reaction mixture was added saturated NH4Cl, and then extracted with EtOAc (2*). The combined organics were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 5% to 60% solvent A/B=hexanes/EtOAc, REDISEP SiO2 120 g). Concentration of appropriate fractions provided Preparation 1B (7.39 g, 86%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ ppm 4.44 (1H, dt, J=8.31, 3.53 Hz), 4.30 (1H, t, J=8.69 Hz), 4.23 (1H, dd, J=9.06, 3.02 Hz), 2.98-3.08 (2H, m), 2.32-2.44 (1H, m, J=13.91, 7.02, 7.02, 4.03 Hz), 2.13-2.25 (2H, m), 1.88-2.00 (2H, m), 0.93 (3H, d, J=7.05 Hz), 0.88 (3H, d, J=6.80 Hz).
7.39 g To a stirred solution of 5,5,5-trifluoropentanoic acid (5.04 g, 32.3 mmol) in DCM (50 mL) and DMF (3 drops) was added oxalyl chloride (3.4 mL, 38.8 mmol) dropwise over 5 min and the solution was stirred until all bubbling subsided. The reaction mixture was concentrated under reduced pressure to give pale yellow oil. To a separate flask charged with a solution of (45)-4-(propan-2-yl)-l,3-oxazolidin-2-one (4.18 g, 32.4 mmol) in THF (100 mL) at -78 C was added n-BuLi (2.5M in hexane) (13.0 mL, 32.5 mmol) dropwise via syringe over 5 min. After stirring for 10 min, the above acid chloride dissolved in THF (20 mL) was added via cannula over 15 min. The reaction mixture was warmed to 0 C, and was allowed to warm to room temperature as the bath warmed and stirred overnight. To the reaction mixture was added saturated NH4C1, and then extracted with EtOAc (2x). The combined organics were washed with brine, dried (Na2S04), filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 5% to 60%> solvent A/B=hexanes/EtOAc, REDISEP Si02 120g). Concentration of appropriate fractions provided Intermediate S-IH (7.39 g, 86%) as a colorless oil: 1H NMR (400 MHz, CDC13) δ ppm 4.44 (1 H, dt, J=8.31, 3.53 Hz), 4.30 (1 H, t, J=8.69 Hz), 4.23 (1 H, dd, J=9.06, 3.02 Hz), 2.98-3.08 (2 H, m), 2.32-2.44 (1 H, m, J=13.91, 7.02, 7.02, 4.03 Hz), 2.13-2.25 (2 H, m), 1.88-2.00 (2 H, m), 0.93 (3 H, d, J=7.05 Hz), 0.88 (3 H, d, J=6.80 Hz).
  • 8
  • [ 407-62-5 ]
  • [ 17016-83-0 ]
  • [ 1401067-00-2 ]
YieldReaction ConditionsOperation in experiment
86% Intermediate S-1H: (4S)-4-(Propan-2-yl)-3-(5,5,5-trifluoropentanoyl)-1,3-oxazolidin-2-one [0285] 5,5,5-trifluoropentanoic acid (5.04 g, 32.3 mmol) in DCM (50 mL) and DMF (3 drops) was added oxalyl chloride (3.4 mL, 38.8 mmol) dropwise over 5 min. The solution was stirred until all bubbling subsided. The reaction mixture was concentrated under reduced pressure to give pale yellow oil. To a separate flask charged with a solution of (4S)-4-(propan-2-yl)-1,3-oxazolidin-2-one (4.18 g, 32.4 mmol) in THF (100 mL) at -78 C. was added n-BuLi (2.5M in hexane) (13.0 mL, 32.5 mmol) dropwise via syringe over 5 min. After stirring for 10 min, the above acid chloride, dissolved in THF (20 mL), was added via cannula over 15 min. The reaction mixture was warmed to 0 C., and was allowed to warm to room temperature as the bath warmed and stirred overnight. To the reaction mixture was added saturated NH4Cl, and the mixture was extracted with EtOAc (2×). The combined organics were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 5% to 60% solvent A/B=hexanes/EtOAc, REDISEP SiO2 120 g). Concentration of the appropriate fractions provided Intermediate S-1H (7.39 g, 86%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ ppm 4.44 (1H, dt, J=8.31, 3.53Hz), 4.30 (1H, t, J=8.69 Hz), 4.23 (1H, dd, J=9.06, 3.02Hz), 2.98-3.08 (2H, m), 2.32-2.44 (1H, m, J=13.91, 7.02, 7.02, 4.03Hz), 2.13-2.25 (2H, m), 1.88-2.00 (2H, m), 0.93 (3H, d, J=7.05 Hz), 0.88 (3H, d, J=6.80 Hz).
86% To a stirred solution of 5,5,5-trifluoropentanoic acid (5.04 g, 32.3 mmol) inDCM (50 mL) and DMF (3 drops) was added oxalyl chloride (3.4 mL, 38.8 mmol)dropwise over 5 min and the solution was stirred until all bubbling subsided. Thereaction mixture was concentrated under reduced pressure to give pale yellow oil. To aseparate flask charged with a solution of ( 48)-4-(propan-2-yl)-I ,3-oxazolidin-2-one ( 4.I820 g, 32.4 mmol) in THF (IOO mL) at -78 oc was added n-BuLi (2.5M in hexane, 13.0 mL,32.5 mmol) dropwise via syringe over 5 min. After stirring for IO min, the above acidchloride dissolved in THF (20 mL) was added via cannula over I5 min. The reactionmixture was warmed to 0 C, and was allowed to warm to room temperature as the bathwarmed and stirred overnight. To the reaction mixture was added saturated NH4Cl, and25 then extracted with EtOAc (2x). The combined organics were washed with brine, dried(Na2S04), filtered and concentrated under reduced pressure. The crude material waspurified by flash chromatography (Teledyne ISCO CombiFlash Rf, 5% to 60% solventA/B=hexanes/EtOAc, REDISEP Si02 I20g). Concentration of appropriate fractionsprovided Intermediate S-IB (7.39 g, 86%) as a colorless oil: 1H NMR (400 MHz, CDCh) 8 ppm 4.44 (I H, dt, J=8.3I, 3.53 Hz), 4.30 (I H, t, J=8.69 Hz), 4.23 (I H, dd, J=9.06,3.02 Hz), 2.98-3.08 (2 H, m), 2.32-2.44 (I H, m, J=13.9I, 7.02, 7.02, 4.03 Hz), 2.13-2.25(2 H, m), 1.88-2.00 (2 H, m), 0.93 (3 H, d, J=7.05 Hz), 0.88 (3 H, d, J=6.80 Hz).
86% [00141] To a stirred solution of 5,5,5-trifluoropentanoic acid (5.04 g, 32.3 mmol) inDCM (50 mL) and DMF (3 drops) was added oxalyl chloride (3.4 mL, 38.8 mmol)dropwise over 5 min. The solution was stirred until all bubbling subsided. The reactionmixture was concentrated under reduced pressure to give a pale yellow oil. To a separateflask, charged with a solution of ( 48)-4-(propan-2-yl)-1 ,3-oxazolidin-2-one ( 4.18 g, 32.420 mmol) in THF (100 mL) at -78 oc was added n-BuLi (13.0 mL, 32.5 mmol, 2.5M inhexane) dropwise via syringe over 5 min. After stirring for 1 0 min, the above acidchloride, dissolved in THF (20 mL ), was added via cannula over 15 min. The reactionmixture was warmed to 0 oc and was allowed to warm to room temperature as the bathwarmed and stirred overnight. To the reaction mixture was then added saturated NH4Cl,25 and it was then extracted with EtOAc (2x). The combined organics were washed withbrine, dried (Na2S04), filtered and concentrated under reduced pressure. The crudematerial was purified by silica gel chromatography (hexanes/EtOAc) to provideIntermediate S-1G (7.39 g, 86%) as a colorless oil: 1H NMR (400 MHz, CDCh) 8 4.44 (1H, dt, J=8.31, 3.53 Hz), 4.30 (1 H, t, J=8.69 Hz), 4.23 (1 H, dd, J=9.06, 3.02 Hz), 2.98-3.08 (2 H, m), 2.32-2.44 (1 H, m, J=13.91, 7.02, 7.02, 4.03 Hz), 2.13-2.25 (2 H, m), 1.88-2.00 (2 H, m), 0.93 (3 H, d, J=7.05 Hz), 0.88 (3 H, d, J=6.80 Hz).
86% Preparation A-i B: (4S)-4-(Propan-2-yl)-3 -(5,5,5 -trifluoropentanoyl)- 1,3 -oxazolidin-2- one [00143j To a stirred solution of 5,5,5-trifluoropentanoic acid (5.04 g, 32.3 mmol) in DCM (50 mL) and DMF (3 drops) was added oxalyl chloride (3.4 mL, 38.8 mmol) dropwise over 5 mm and the solution was stirred until all bubbling subsided. The reaction mixture was concentrated under reduced pressure to give pale yellow oil. To a separate flask charged with a solution of (4S)-4-(propan-2-yl)- 1 ,3-oxazolidin-2-one (4.18g, 32.4 mmol) in THF (100 mL) at -78 C was added n-BuLi (2.5M in hexane) (13.0 mL,32.5 mmol) dropwise via syringe over 5 mm. After stirring for 10 mm, the above acid chloride dissolved in THF (20 mL) was added via cannula over 15 mm. The reaction mixture was warmed to 0 C, and was allowed to warm to room temperature as the bath warmed and stirred overnight. To the reaction mixture was added saturated NH4C1, andthe mixture was then extracted with EtOAc (2x). The combined organics were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 5% to 60% solvent A/B=hexanes/EtOAc, REDISEP Si02 120g). Concentration of appropriate fractions provided Preparation A-lB (7.39 g, 86%) as a colorless oil: ‘HNMR (400 MHz, CDC13) ö ppm 4.44 (1 H, dt, J8.31, 3.53 Hz), 4.30 (1 H, t, J8.69 Hz),4.23 (1 H, dd, J=9.06, 3.02 Hz), 2.98-3.08 (2 H, m), 2.32-2.44 (1 H, m, J=13.91, 7.02,7.02, 4.03 Hz), 2.13-2.25 (2 H, m), 1.88-2.00 (2 H, m), 0.93 (3 H, d, J=7.05 Hz), 0.88 (3 H, d, J=6.80 Hz).
86% Intermediate S-i H: (4S)-4-(Propan-2-yl)-3 -(5,5,5 -trifluoropentanoyl)- 1,3 -oxazolidin-2- one[00146j To a stirred solution of 5,5,5-trifluoropentanoic acid (5.04 g, 32.3 mmol) in DCM (50 mL) and DMF (3 drops) was added oxalyl chloride (3.4 mL, 38.8 mmol) dropwise over 5 mm and the solution was stirred until all bubbling subsided. The reaction mixture was concentrated under reduced pressure to give pale yellow oil. To a separate flask charged with a solution of (4S)-4-(propan-2-yl)- 1 ,3-oxazolidin-2-one (4.18g, 32.4 mmol) in THF (100 mL) at -78 C was added n-BuLi (2.5M in hexane) (13.0 mL,32.5 mmol) dropwise via syringe over 5 mm. After stirring for 10 mm, the above acid chloride dissolved in THF (20 mL) was added via cannula over 15 mm. The reaction mixture was warmed to 0 C, and was allowed to warm to room temperature as the bath warmed and stirred overnight. To the reaction mixture was added saturated NH4C1, andthen extracted with EtOAc (2x). The combined organics were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (Teledyne ISCO CombiFlash Rf, 5% to 60% solvent A/B=hexanes/EtOAc, REDISEP Si02 1 20g). Concentration of appropriate fractions provided Intermediate S-1H (7.39 g, 86%) as a colorless oil: ‘H NMR (400 MHz, CDC13)o ppm 4.44 (1 H, dt, J=8.31, 3.53 Hz), 4.30 (1 H, t, J=8.69 Hz), 4.23 (1 H, dd, J9.06,3.02 Hz), 2.98-3.08 (2 H, m), 2.32-2.44 (1 H, m, J=13.91, 7.02, 7.02, 4.03 Hz), 2.13-2.25(2 H, m), 1.88-2.00 (2 H, m), 0.93 (3 H, d, J=7.05 Hz), 0.88 (3 H, d, J6.80 Hz).
86% To a stirred solution of 5,5,5-trifluoropentanoic acid (5.04 g, 32.3 mmol) inDCM (50 mL) and DMF (3 drops) was added oxalyl chloride (3.4 mL, 38.8 mmol)dropwise over 5 min. The solution was stirred until all bubbling subsided. The reaction5 mixture was concentrated under reduced pressure to give a pale yellow oil. To a separateflask charged with a solution of ( 48)-4-(propan-2-yl)-1 ,3-oxazolidin-2-one ( 4.18 g, 32.4mmol) in THF (100 mL) at -78 oc was added n-BuLi (13.0 mL, 32.5 mmol, 2.5M inhexane) dropwise via syringe over 5 min. After stirring for 1 0 min, the above acidchloride dissolved in THF (20 mL) was added via cannula over 15 min. The reaction10 mixture was warmed to 0 C, and was allowed to warm to room temperature as the bathwarmed and stirred overnight. To the reaction mixture was added saturated NH4Cl, andthen extracted with EtOAc (2x). The combined organics were washed with brine, dried(Na2S04), filtered and concentrated under reduced pressure. The crude material waspurified by silica gel chromatography (hexanes/EtOAc) to provide Intermediate S IA15 (7.39 g, 86%) as a colorless oil: 1H NMR (400 MHz, CDCh) 8 4.44 (1 H, dt, J=8.31, 3.53Hz), 4.30 (1 H, t, J=8.69 Hz), 4.23 (1 H, dd, J=9.06, 3.02 Hz), 2.98-3.08 (2 H, m), 2.32-2.44 (1 H, m, J=13.91, 7.02, 7.02, 4.03 Hz), 2.13-2.25 (2 H, m), 1.88-2.00 (2 H, m), 0.93(3 H, d, J=7.05 Hz), 0.88 (3 H, d, J=6.80 Hz).

  • 9
  • [ 5928-51-8 ]
  • [ 17016-83-0 ]
  • [ 138296-00-1 ]
YieldReaction ConditionsOperation in experiment
97% To 2-thiophene-propionic acid 28 (5.23 g, 33.5 mmol) in THF (60 mL) were added Et3N (5.6 mL, 40 mmol) and isobutylchloroformate (5.0 mL, 36.8 mmol) at 0 C. After stirring for 30 min, the mixture was added to the lithio-(4S)-4-isopropyl-2-oxazolidinone, prepared by dropwise addition of n-BuLi (14.2 mL, 36.8 mmol, 2.6 mol/L in hexane) to (4S)-4-isopropyl-2-oxazolidinone (4.76 g, 36.8 mmol) in THF (60 mL) at -78 C, and the mixture was stirred for 1 h. The reaction was quenched with saturated aqueous NaHCO3 and the whole was extracted with EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography (hexane/EtOAc = 5:1) to yield 30 (3.68 g, 97%). [alpha]D28 +78 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3): delta 7.12 (dd, J = 5.2, 1.2 Hz, 1H), 6.91 (dd, J = 5.2, 3.2 Hz, 1H), 6.86-6.85 (m, 1H), 4.44 (td, J = 8.1, 3.6 Hz, 1H), 4.26 (dd, J = 9.2, 8.0 Hz, 1H), 4.21 (dd, J = 9.2, 3.2 Hz, 1H), 3.41-3.25 (m, 2H), 3.24-3.19 (m, 2H), 2.41-2.33 (m, 1H), 0.91 (d, J = 6.8 Hz, 3H), 0.85 (d, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): delta 171.7, 153.9, 143.0, 126.7, 124.8, 123.4, 63.4, 58.3, 37.2, 28.2, 24.3, 17.8, 14.5; HRMS (EI) Calcd for C13H17NO3S [M]+: 267.0929. Found: 267.0933.
  • 10
  • [ 5928-51-8 ]
  • [ 17016-83-0 ]
  • (S)-3-{(2S,3R)-3-hydroxy-2-(thiophen-2-ylmethyl)pent-4-enoyl}-4-isopropyloxazolidin-2-one [ No CAS ]
  • 11
  • [ 16957-70-3 ]
  • [ 17016-83-0 ]
  • N-(2'-methyl-2'E-pentenoyl)-4S-isopropyl-1,3-oxazolidin-2-one [ No CAS ]
 

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