[ CAS No. 25462-85-5 ] {[proInfo.proName]}

Name: 25462-85-5|2-Chloro-6-methylisonicotinic acid|98%
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SKU: A108650
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Product Details of [ 25462-85-5 ]

CAS No. :	25462-85-5	MDL No. :	MFCD00052830
Formula :	C₇H₆ClNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZGZMEKHQIZSZOH-UHFFFAOYSA-N
M.W :	171.58	Pubchem ID :	141209
Synonyms :

Calculated chemistry of [ 25462-85-5 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	41.17
TPSA :	50.19 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) :	-6.11 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.3
Log Po/w (XLOGP3) :	1.74
Log Po/w (WLOGP) :	1.74
Log Po/w (MLOGP) :	-0.18
Log Po/w (SILICOS-IT) :	1.82
Consensus Log Po/w :	1.28

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-2.34
Solubility :	0.789 mg/ml ; 0.0046 mol/l
Class :	Soluble
Log S (Ali) :	-2.41
Solubility :	0.666 mg/ml ; 0.00388 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.4
Solubility :	0.688 mg/ml ; 0.00401 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.62

Safety of [ 25462-85-5 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H317-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 25462-85-5 ]

* 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 [ 25462-85-5 ]
Downstream synthetic route of [ 25462-85-5 ]

[ 25462-85-5 ] Synthesis Path-Upstream 1~11

1
[ 86454-13-9 ]
[ 25462-85-5 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 14, p. 4629 - 4635

2
[ 3998-90-1 ]
[ 25462-85-5 ]

Reference： [1] Journal of the American Chemical Society, 1959, vol. 81, p. 704,707

3
[ 98491-78-2 ]
[ 25462-85-5 ]

Reference： [1] Journal of the American Chemical Society, 1959, vol. 81, p. 704,707

4
[ 18619-97-1 ]
[ 25462-85-5 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 14, p. 4629 - 4635

5
[ 25462-85-5 ]
[ 79-37-8 ]
[ 3998-90-1 ]

Reference： [1] Patent: US5962458, 1999, A,

6
[ 67-56-1 ]
[ 25462-85-5 ]
[ 3998-90-1 ]

Yield	Reaction Conditions	Operation in experiment
2 g	at -5 - 20℃; for 24 h; Inert atmosphere	General procedure: To a stirred solution of POCl₃ (10 mL, 107 mmol) was added acid 2 (2.37 g, 15.5 mmol), and the resulting solution was heated to reflux for 18 h. The excess POCl₃ was removed under reduced pressure, the residue was cooled to -5°C, methanol (20 mL) was added drop wise, and the resulting mixture was stirred for 24 h at rt. Distilled off MeOH completely, neutralized with solid NaHCO3, and partitioned between H₂O (30 mL) and EtOAc (30 mL). The aqueous layer was extracted with EtOAc, dried (Na₂SO₄), and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography over silica gel (CH₂Cl₂), to give ester 3a (2 g, 10.8 mmol, 69percent yield) as a white solid. R_f (Silica gel, CH₂Cl₂): 0.66; ¹H NMR (300 MHz, CDCl₃) δ 2.59 (s, 3H), 3.94 (s, 3H), 7.61(s, 1H), 7.67 (s, 1H); ¹³C NMR (75 MHz, CDCl₃) δ 24.2, 52.9, 120.8, 121.2, 140.3, 151.4, 160.5, 164.6; MS (EI, 70ev): m/z (percent) [M+H]⁺^. 186 (100).

Reference： [1] Tetrahedron Letters, 2007, vol. 48, # 6, p. 999 - 1002
[2] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 14, p. 4629 - 4635
[3] Chemistry - A European Journal, 2015, vol. 21, # 33, p. 11745 - 11756

7
[ 25462-85-5 ]
[ 3998-90-1 ]

Reference： [1] Patent: US5968875, 1999, A,

8
[ 186581-53-3 ]
[ 25462-85-5 ]
[ 3998-90-1 ]

Reference： [1] Patent: WO2008/46226, 2008, A1, . Location in patent: Page/Page column 38; 39

9
[ 25462-85-5 ]
[ 64-17-5 ]
[ 3998-88-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	at 0 - 80℃;	Step 1: Ethyl 2-chloro-6-methylisonicotinate (97). To a stirred solution of 96 (7.0 g, 40.79 mmol) in ethanol (70 mL) was added conc H₂SO₄ (2 mL) at 0° C. dropwise followed by heating at 80° C. for 12 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The resulting residue was diluted with ethyl acetate and washed with water, sodium bicarbonate solution and sat. NaCl. The organic layer was dried over anhydrous Na₂SO₄ and concentrated to afford 97 (7 g, 86percent) as a white solid.

Reference： [1] Patent: US2010/249071, 2010, A1, . Location in patent: Page/Page column 63-64
[2] Patent: WO2008/29371, 2008, A1, . Location in patent: Page/Page column 41
[3] Patent: WO2009/24905, 2009, A1, . Location in patent: Page/Page column 38-39; 49
[4] Patent: US2010/63108, 2010, A1, . Location in patent: Page/Page column 16
[5] Patent: US2011/46170, 2011, A1, . Location in patent: Page/Page column 17
[6] Patent: US2011/46170, 2011, A1, . Location in patent: Page/Page column 18
[7] Patent: US2011/212998, 2011, A1, . Location in patent: Page/Page column 14
[8] Patent: WO2009/109907, 2009, A1, . Location in patent: Page/Page column 42

10
[ 25462-85-5 ]
[ 7664-93-9 ]
[ 3998-88-7 ]

Reference： [1] Patent: US5962458, 1999, A,

11
[ 25462-85-5 ]
[ 3998-88-7 ]

Reference： [1] Patent: US6362336, 2002, B1, . Location in patent: Example 43

[ 25462-85-5 ] Synthesis Path-Downstream 1~88

1
[ 3998-90-1 ]
[ 25462-85-5 ]

Reference： [1]Journal of the American Chemical Society,1959,vol. 81,p. 704,707

2
[ 25462-85-5 ]
[ 873-63-2 ]
[ 879222-11-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1892 - 1897

3
[ 25462-85-5 ]
[ 64-17-5 ]
[ 3998-88-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sulfuric acid; at 0 - 80℃;	Step 1: Ethyl 2-chloro-6-methylisonicotinate (97). To a stirred solution of 96 (7.0 g, 40.79 mmol) in ethanol (70 mL) was added conc H2SO4 (2 mL) at 0 C. dropwise followed by heating at 80 C. for 12 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The resulting residue was diluted with ethyl acetate and washed with water, sodium bicarbonate solution and sat. NaCl. The organic layer was dried over anhydrous Na2SO4 and concentrated to afford 97 (7 g, 86%) as a white solid.
		a) A solution of 2-chloro-6-methylisonicotinic acid (15.5 g, 90.3 mmol, 1 equivalent) in EtOH (200 ml.) and a few drops of concentrated sulfuric acid is stirred at 75C for 24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (200 ml.) and washed with a solution of sat. aq. NaHCO3 (70 ml.) and water (2x70 ml_). The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6-methylisonicotinic acid ethyl ester (16.3 g) as a pink powder; LC-MS: tR = 0.92 min, [M+1]+ = 200.17.
		A solution of 2-chloro-6-methylisonicotinic acid (15.5 g, 90.3 mmol, 1 eq.) in ethanol (200 mL) and a few drops of concentrated sulfuric acid is stirred at 75C for24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (200 mL) and washed with a solution of sat. aq. NaHCO3 (70 mL) and water (2x70 mL). <n="40"/>The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6- methylisonicotinic acid ethyl ester (16.3 g) as a pink powder; LC-MS: tR = 0.92 min, [M+1]+ = 200.17; A solution of 2-chloro-6-methyl-isonicotinic acid (15.5 g, 90.3 mmol) in ethanol (200 mL) and H2SO4 (0.5 mL) is stirred at 75C for 24 h. The solvent is evaporated and the residue is dissolved in EA (200 mL). The solution is washed with sat. aq. NaHCO3-solution (70 mL) and water (70 mL), dried over MgSO4, filtered, concentrated and dried under HV to give 2-chloro-6-methyl-isonicotinic acid ethyl ester (16.3 g) as a pink powder; LC-MS: tR = 0.92 min; [M+1]+ = 200.17.

		A solution of 2-chloro-6-methylisonicotinic acid (15.5 g, 90.3 mmol, 1 equivalent) in EtOH (200 mL) and a few drops of concentrated sulfuric acid is stirred at 75 C. for 24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (200 mL) and washed with a solution of sat. aq. NaHCO3 (70 mL) and water (2×70 mL). The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6-methylisonicotinic acid ethyl ester (16.3 g) as a pink powder; LC-MS: tR=0.92 min, [M+1]+=200.17.
		a) To a solution of 2-chloro-6-methylisonicotinic acid (50 g, 291.4 mmol) in ethanol (750 mL), a few drops of concentrated sulfuric acid are added and the mixture is stirred at 75 C. for 24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (300 mL) and washed with a solution of sat. aq. NaHCO3 (100 mL) followed with brine (2*70 mL). The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6-methylisonicotinic acid ethyl ester (54.9 g) as a white solid after recrystallization from heptane; LC-MS: tR=0.92 min, [M+1]+=200.17.
		a) Concentrated H2SO4 (1.16 mL, 21.6 mmol) is added dropwise to a suspension of 2-chloro-6-methylpyridine-4-carboxylic acid (11.58 g, 67.49 mmol) in ethanol (100 mL). The reaction mixture is then stirred at 70 C. for 24 h. Sat. NaHCO3 is added slowly to reach pH 8 and the aq. solution is extracted with EA three times. The org. extracts are collected, dried over MgSO4, filtered and evaporated to give 2-chloro-6-methylpyridine-4-carboxylic acid ethyl ester (11.81 g) as an off white solid; LC-MS: tR=0.91 min, [M+H]+=199.93.
	With sulfuric acid; In ethanol; at 75℃; for 24h;Product distribution / selectivity;	a) A solution of 2-chloro-6-methylisonicotinic acid (15.5 g, 90.3 mmol, 1 eq.) in ethanol (200 mL) and a few drops of concentrated sulfuric acid is stirred at 75 C. for 24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (200 mL) and washed with a solution of sat. aq. NaHCO3 (70 mL) and water (2*70 mL). The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6-methylisonicotinic acid ethyl ester (16.3 g) as a pink powder; LC-MS: tR=0.92 min, [M+1]+=200.17.
		To a solution of 2-chloro-6-methylisonicotinic acid (50 g, 291.4 mmol) in ethanol (750 ml_), a few drops of concentrated sulfuric acid are added and the mixture is stirred at 75C for 24 h. The solvent is evaporated and the residue is dissolved in ethyl acetate (300 ml.) and washed with a solution of sat. aq. NaHCO3 (100 ml.) followed with brine (2x70 ml_). The org. extract is dried over MgSO4, filtered and evaporated to give 2-chloro-6- methylisonicotinic acid ethyl ester (54.9 g) as a white solid after recrystallization from heptane; LC-MS: tR = 0.92 min, [M+1]+ = 200.17.

Reference： [1]Patent: US2010/249071,2010,A1 .Location in patent: Page/Page column 63-64
[2]Patent: WO2008/29371,2008,A1 .Location in patent: Page/Page column 41
[3]Patent: WO2009/24905,2009,A1 .Location in patent: Page/Page column 38-39; 49
[4]Patent: US2010/63108,2010,A1 .Location in patent: Page/Page column 16
[5]Patent: US2011/46170,2011,A1 .Location in patent: Page/Page column 17
[6]Patent: US2011/46170,2011,A1 .Location in patent: Page/Page column 18
[7]Patent: US2011/212998,2011,A1 .Location in patent: Page/Page column 14
[8]Patent: WO2009/109907,2009,A1 .Location in patent: Page/Page column 42

4
[ 25462-85-5 ]
[ 64-17-5 ]
[ 1011264-05-3 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of K-tert.-butylate (1.99 g, 17.7 mmol) in EtOH (25 ml_), 2-chloro-6-methyl- isonicotinic acid is added. The reaction mixture is stirred at 900C for 7 days. The mixture is cooled to rt, diluted with water and extracted with ether (3x50 ml_). The aq. phase is acidified by adding 1 N aq. HCI and is then extracted three more times with ether (3x30 ml_). The org. extracts are combined, dried over Na2SO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 1 :1 to give 2-ethoxy-6- methyl-isonicotinic acid (237 mg) as a white powder, LC-MS: tR = 0.60 min; [M+1]+ = 182.24; 1H NMR (CD3OD): delta 7.27 (s, 1 H), 7.04 (s, 1 H), 4.33 (q, J = 7.0 Hz, 2 H), 2.46 (s, 3 H), 1.37 (t, J = 7.0 Hz, 3 H).
		To a solution of K-tert.-butylate (1.99 g, 17.7 mmol) in ethanol (25 ml_), 2-chloro-6- methyl-isonicotinic acid is added. The reaction mixture is stirred at 900C for 7 days. The mixture is cooled to rt, diluted with water and extracted with diethyl ether (3x50 ml_). The aq. phase is acidified by adding 1 N aq. HCI and is then extracted three more times with diethyl ether (3x30 ml_). The org. extracts are combined, dried over Na2SO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 1 :1 to give 2-ethoxy-6-methyl-isonicotinic acid (237 mg) as a white powder, LC-MS: tR = 0.60 min; [IVM]+ = 182.24; 1H NMR (CD3OD): delta 7.27 (s, 1 H), 7.04 (s, 1 H), 4.33 (q, J = 7.0 Hz, 2 H), 2.46 (s, 3 H), 1.37 (t, J = 7.0 Hz, 3 H).
		To a solution of K-tert.-butylate (1.99 g, 17.7 mmol) in EtOH (25 mL), 2-chloro-6-methyl-isonicotinic acid is added. The reaction mixture is stirred at 90 C. for 7 days. The mixture is cooled to rt, diluted with water and extracted with ether (3×50 mL). The aq. phase is acidified by adding 1 N aq. HCl and is then extracted three more times with ether (3×30 mL). The org. extracts are combined, dried over Na2SO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 1:1 to give 2-ethoxy-6-methyl-isonicotinic acid (237 mg) as a white powder, LC-MS: tR=0.60 min; [M+1]+=182.24; 1H NMR (CD3OD): delta 7.27 (s, 1H), 7.04 (s, 1H), 4.33 (q, J=7.0 Hz, 2H), 2.46 (s, 3H), 1.37 (t, J=7.0 Hz, 3H).

With potassium tert-butylate; at 90℃; for 168h;

To a solution of K-tert.-butylate (1.99 g, 17.7 mmol) in ethanol (25 mL), 2-chloro-6-methyl-isonicotinic acid is added. The reaction mixture is stirred at 90 C. for 7 days. The mixture is cooled to rt, diluted with water and extracted with diethyl ether (3*50 mL). The aq. phase is acidified by adding 1 N aq. HCl and is then extracted three more times with diethyl ether (3*30 mL). The org. extracts are combined, dried over Na2SO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 1:1 to give 2-ethoxy-6-methyl-isonicotinic acid (237 mg) as a white powder, LC-MS: tR=0.60 min; [M+1]+=182.24; 1H NMR (CD3OD): delta 7.27 (s, 1H), 7.04 (s, 1H), 4.33 (q, J=7.0 Hz, 2H), 2.46 (s, 3H), 1.37 (t, J=7.0 Hz, 3H).

Reference： [1]Patent: WO2008/29371,2008,A1 .Location in patent: Page/Page column 45
[2]Patent: WO2009/24905,2009,A1 .Location in patent: Page/Page column 47
[3]Patent: US2010/63108,2010,A1 .Location in patent: Page/Page column 18
[4]Patent: US2011/212998,2011,A1 .Location in patent: Page/Page column 17

5
[ 25462-85-5 ]
[ 67-63-0 ]
[ 907545-65-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; at 20 - 90℃; for 52h;	a) To a suspension of 2-chloro-6-methyl-isonicotinic acid (20.0 g, 1 17 mmol) in isopropanol (80 ml_), H2SO4 (5 ml.) is added dropwise. The mixture becomes warm (400C). The mixture is stirred for 24 h at rt, then at 900C for 28 h before the solvent is removed in vacuo. The residue is dissolved in ether (200 ml_), washed with sat. aq. NaHCO3-solution (3x50 ml.) followed by brine (3x50 ml_), dried over Na2SO4, filtered and concentrated to give 2-chloro- 6-methyl-isonicotinic acid isopropyl ester (21.0 g) as a colourless oil which slowly crystallises; LC-MS: tR = 0.97 min, [M+1]+ = 214.05.
		To a suspension of 2-chloro-6-methyl-isonicotinic acid (20.0 g, 117 mmol) in isopropanol (80 ml_), H2SO4 (5 ml_) is added dropwise. The mixture becomes warm (400C). The mixture is stirred for 24 h at rt, then at 900C for 28 h before the solvent is removed in vacuo. The residue is dissolved in diethyl ether (200 ml_), washed with sat. aq. NaHCO3-solution (3x50 ml_) followed by brine (3x50 ml_), dried over Na2SO4, filtered and concentrated to give 2-chloro-6-methyl-isonicotinic acid isopropyl ester (21.0 g) as a colourless oil which slowly crystallises; LC-MS: tR = 0.97 min, [M+1]+ = 214.05.
		To a suspension of 2-chloro-6-methyl-isonicotinic acid (20.0 g, 117 mmol) in isopropanol (80 mL), H2SO4 (5 mL) is added dropwise. The mixture becomes warm (40 C.). The mixture is stirred for 24 h at rt, then at 90 C. for 28 h before the solvent is removed in vacuo. The residue is dissolved in ether (200 mL), washed with sat. aq. NaHCO3-solution (3×50 mL) followed by brine (3×50 mL), dried over Na2SO4, filtered and concentrated to give 2-chloro-6-methyl-isonicotinic acid isopropyl ester (21.0 g) as a colourless oil which slowly crystallises; LC-MS: tR=0.97 min, [M+1]+=214.05.

With sulfuric acid; at 20 - 90℃; for 52h;

a) To a suspension of 2-chloro-6-methyl-isonicotinic acid (20.0 g, 117 mmol) in isopropanol (80 mL), H2SO4 (5 mL) is added dropwise. The mixture becomes warm (40 C.). The mixture is stirred for 24 h at rt, then at 90 C. for 28 h before the solvent is removed in vacuo. The residue is dissolved in diethyl ether (200 mL), washed with sat. aq. NaHCO3-solution (3*50 mL) followed by brine (3*50 mL), dried over Na2SO4, filtered and concentrated to give 2-chloro-6-methyl-isonicotinic acid isopropyl ester (21.0 g) as a colourless oil which slowly crystallises; LC-MS: tR=0.97 min, [M+1]+=214.05.

Reference： [1]Patent: WO2008/29371,2008,A1 .Location in patent: Page/Page column 46
[2]Patent: WO2009/24905,2009,A1 .Location in patent: Page/Page column 42
[3]Patent: US2010/63108,2010,A1 .Location in patent: Page/Page column 18-19
[4]Patent: US2011/212998,2011,A1 .Location in patent: Page/Page column 15
[5]Journal of Medicinal Chemistry,2014,vol. 57,p. 110 - 130

6
[ 25462-85-5 ]
[ 1010113-34-4 ]
[ 1011264-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 1h;	a) A solution of 2-chloro-6-methyl-isonicotinic acid (227 mg, 1.33 mmol), PyBOP (700 mg, 1.34 mmol), DIPEA (860 mg, 6.64 mmol), and 4-allyloxy-N-hydroxy-3,5-dimethyl- benzamidine (410 mg, 1.86 mmol) in DCM (7 ml.) is stirred at rt for 1 h. The mixture is diluted with ether, washed with 1 N aq. HCI (2x25 ml_), 1 N aq. KHSO4 solution (2x25 ml.) and brine (25 ml_), dried over Na2SO4, filtered and concentrated. The crude product is purified by MPLC on silica gel eluting with a gradient of EA in heptane to give 2-chloro-6- methyl-isonicotinic acid (4-allyloxy-N-hydroxy-3,5-dimethyl-benzamidine) ester (142 mg) as a colourless resin; LC-MS: tR = 1.04 min, [M+1]+ = 374.10.

Reference： [1]Patent: WO2008/29371,2008,A1 .Location in patent: Page/Page column 62

7
[ 67-56-1 ]
[ 25462-85-5 ]
[ 3998-90-1 ]

Yield	Reaction Conditions	Operation in experiment
2 g	at -5 - 20℃; for 24h;Inert atmosphere;	General procedure: To a stirred solution of POCl3 (10 mL, 107 mmol) was added acid 2 (2.37 g, 15.5 mmol), and the resulting solution was heated to reflux for 18 h. The excess POCl3 was removed under reduced pressure, the residue was cooled to -5°C, methanol (20 mL) was added drop wise, and the resulting mixture was stirred for 24 h at rt. Distilled off MeOH completely, neutralized with solid NaHCO3, and partitioned between H2O (30 mL) and EtOAc (30 mL). The aqueous layer was extracted with EtOAc, dried (Na2SO4), and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography over silica gel (CH2Cl2), to give ester 3a (2 g, 10.8 mmol, 69percent yield) as a white solid. Rf (Silica gel, CH2Cl2): 0.66; 1H NMR (300 MHz, CDCl3) delta 2.59 (s, 3H), 3.94 (s, 3H), 7.61(s, 1H), 7.67 (s, 1H); 13C NMR (75 MHz, CDCl3) delta 24.2, 52.9, 120.8, 121.2, 140.3, 151.4, 160.5, 164.6; MS (EI, 70ev): m/z (percent) [M+H]+. 186 (100).

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 999 - 1002
[2]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4629 - 4635
[3]Chemistry - A European Journal,2015,vol. 21,p. 11745 - 11756

8
[ 25462-85-5 ]
[ 928306-83-6 ]