Home Cart 0 Sign in  

[ CAS No. 26218-80-4 ]

{[proInfo.proName]} ,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
2D
Chemical Structure| 26218-80-4
Chemical Structure| 26218-80-4
Structure of 26218-80-4 *Storage: {[proInfo.prStorage]}

Quality Control of [ 26218-80-4 ]

Related Doc. of [ 26218-80-4 ]

SDS
Alternatived Products of [ 26218-80-4 ]
Alternatived Products of [ 26218-80-4 ]

Product Details of [ 26218-80-4 ]

CAS No. :26218-80-4MDL No. :MFCD00674130
Formula : C8H9NO3 Boiling Point : -
Linear Structure Formula :-InChI Key :-
M.W :167.16Pubchem ID :586039
Synonyms :

Computed Properties of [ 26218-80-4 ]

TPSA : 48.4 H-Bond Acceptor Count : 4
XLogP3 : 1 H-Bond Donor Count : 0
SP3 : 0.25 Rotatable Bond Count : 3

Safety of [ 26218-80-4 ]

Signal Word:WarningClass:N/A
Precautionary Statements:P261-P305+P351+P338UN#:N/A
Hazard Statements:H315-H319-H335Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 26218-80-4 ]

  • Upstream synthesis route of [ 26218-80-4 ]
  • Downstream synthetic route of [ 26218-80-4 ]

[ 26218-80-4 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 67-56-1 ]
  • [ 93-60-7 ]
  • [ 33402-75-4 ]
  • [ 5470-70-2 ]
  • [ 67367-26-4 ]
  • [ 26218-80-4 ]
Reference: [1] Chemistry Letters, 1980, p. 131 - 134
[2] Chemistry Letters, 1980, p. 131 - 134
[3] Bulletin of the Chemical Society of Japan, 1981, vol. 54, # 6, p. 1761 - 1766
  • 2
  • [ 67-56-1 ]
  • [ 93-60-7 ]
  • [ 33402-75-4 ]
  • [ 5470-70-2 ]
  • [ 67367-26-4 ]
  • [ 26218-80-4 ]
Reference: [1] Chemistry Letters, 1980, p. 131 - 134
[2] Chemistry Letters, 1980, p. 131 - 134
[3] Bulletin of the Chemical Society of Japan, 1981, vol. 54, # 6, p. 1761 - 1766
  • 3
  • [ 26218-80-4 ]
  • [ 66171-50-4 ]
Reference: [1] Heterocycles, 1993, vol. 36, # 2, p. 323 - 328
  • 4
  • [ 26218-80-4 ]
  • [ 65873-72-5 ]
Reference: [1] Tetrahedron, 1992, vol. 48, # 8, p. 1457 - 1464
[2] Patent: WO2015/158427, 2015, A1,
  • 5
  • [ 26218-80-4 ]
  • [ 58584-63-7 ]
YieldReaction ConditionsOperation in experiment
100% With sodium bis(2-methoxyethoxy)aluminium dihydride In tert-butyl methyl ether; toluene at 0℃; for 1.63333 h; Preparation Example 1
Synthesis of (6-methoxypyridin-3-yl)methanol (2)
To a solution of methyl-6-methoxynicotinate (1) (650 g, 3.89 mol) in t-butyl methyl ether (hereinafter abbreviated as "MTBE") (6.5 L) cooled in an ice bath was added sodium bis(2-methoxyethoxy)aluminum hydride (65percent solution in toluene, 1.45 kg, 4.67 mol) under a nitrogen atmosphere over a period of 1.3 hours.
After stirring for 20 minutes, a 3.5 N aqueous solution of sodium hydroxide (2.6 L) was added to the reaction mixture while keeping the temperature 15° C. or below.
The reaction mixture was stirred at 32° C. for 45 minutes and then the organic layer was separated and the aqueous layer was re-extracted with MTBE (2.3 L).
The organic layers were combined and concentrated under reduced pressure to dryness, and then toluene (1.3 L) was added to the residue and azeotropic distillation was carried out.
Azeotropic distillation with toluene (1.3 L) was repeated three times to give 597 g of the title compound as a pale yellow oil (yield 100percent).
1H-NMR (CDCl3) δ (ppm): 8.11 (1H, d, J=2.4 Hz), 7.62 (1H, dd, J=2.4 Hz, 8.8 Hz), 6.75 (1H, d, J=8.8 Hz), 4.62 (2H, s), 3.93 (3H, s)
94% at 0 - 25℃; for 72 h; Sodium borohydride (1 1.30 g, 299 mmol) was added to a solution of the methyl 6- methoxynicotinate (5.00 g, 29.9 mmol) in ethanol (100 ml.) at 0°C. The reaction was allowed to warm to room temperature and stirred for 3 days. The reaction was cooled to 0°C and quenched by slow addition of 1 N HCI until pH 4.0. The reaction mixture was concentrated to remove ethanol. The remaining aqueous solution was washed with ethyl acetate (2x), then neutralized with saturated aqueous sodium bicarbonate, then extracted with ethyl acetate (3X). The organic layers were combined, washed with brine, dried (Na2S04), filtered and concentrated. The crude material was purified by silica chromatography (hexanes / ethyl acetate 1 :1 , 3:7) to give a clear oil. Mass/Yield - 3.9 g / 94percent TLC (hexanes/ethyl acetate = 1 :1 ) Rf = 0.22, UV active. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.91 (s, 3 H) 4.61 (s, 2 H) 6.68 - 6.77 (m, 1 H) 7.49 - 7.68 (m, 1 H) 8.09 (s, 1 H).
89%
Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 1 h;
Stage #2: With sodium hydroxide In tetrahydrofuran; water
2 To a stirred suspension of LiAlH4 (11.4 g, 300 mmol) in THF (300 mL) at 0 °C was slowly added a solution of methyl 6-methoxynicotinate (50.0 g, 299 mmol). After stirring for 1 h at 0 °C, 10percent NaOH aq. (25.0 mL) and Na2SO4 were added. The resulting precipitate was removed by filtration through a pad of Celite.(R). and the filtrate was concentrated in vacuo to give the title compound as a colorless oil (41.1 g, 268 mmol, 89percent). 1H NMR (CDCl3, 400 MHz): δ 1.75 (1H, brs), 3.94 (3H, s), 4.62 (2H, s), 6.75 (1H, d, J = 8.0 Hz), 7.62 (1H, dd, J = 8.0, 2.4 Hz), 8.12 (1H, d, J = 2.4 Hz).
86% With methanol; sodium tetrahydroborate In tetrahydrofuran at 23℃; for 12 h; (A) To a stirred solution of methyl 6-methoxynicotinate (14 g, 83.83 mmol, 1.0 eq) in THE (300 ml), NaBH4 (47.7 g, 1.257 mol, 15 eq) was added at RT, followed by MeOH (300 ml). The RM was stirred atRT for 12 h. Reaction progress was monitored by TLC. The RM was quenched with sat. NH4CI (100 ml), diluted with water (100 ml) and extracted with EtOAc (3 x 200 ml). The organic layer was washed with brine solution (100 ml), dried (Na2504), filtered and concentrated to afford the crude product, which upon CC (silica gel, 40percent EtOAc in PE afforded (6-methoxypyridin-3-yl)methanol (10 g, 86percent).
83% With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere Under nitrogen, a suspension of lithium aluminium hydride solution in THF (1M, 6.58mL, 6.58mmol) in THF (3.39mL) was stirred at 0°C for 5min. Methyl 6-methoxynicotinate 2b (1.0g, 5.98mmol) was added portionwise and the mixture was stirred for 10m. The suspension was allowed to warm to room temperature and stirred for 2h before the solution was cooled to 0°C. The suspension was carefully quenched with water (0.04mL), 15percent NaOH (0.04mL) followed by water (0.12mL). The resulting precipitate was filtered with Celite and washed with ethyl acetate. The filtrate was concentrated under reduced pressure to give product 2c (0.690g, 4.96mmol, 83percent yield) as a yellow oil; (found (ESI): M++H, 140.0711. C7H10NO2 requires M, 140.0706); νmax 3298, 2945, 1608, 1573, 1492cm−1; δH (400MHz, DMSO) 8.07 (1H, s, H3), 7.64 (1H, d, J 8.5, H2), 6.77 (1H, d, J 8.5, H1), 5.11 (1H, t, J 5.6, OH), 4.43 (2H, d, J 5.6, H4), 3.83 (3H, s, CH3); δC (101MHz, DMSO) 162.7, 144.00, 138.3, 130.6, 109.9, 60.2, 52.9; m/z (ESI) 139.8 (M++1).
72%
Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; for 2.66667 h;
Stage #2: at 20℃; for 0.333333 h;
Step 1:
(6-Methoxy-pyridin-3-yl)-methanol
A solution of methyl 6-methoxynicotinate (3.00 g, 17.9 mmol) in tetrahydrofuran (10 mL) was added via an addition funnel over a period of 10 min to a cooled (0° C.) mixture of lithium aluminum hydride (817 mg, 21.5 mmol) in tetrahydrofuran (18 mL).
The mixture was stirred at 0° C. for 30 min and then at room temperature for 2 h.
The reaction mixture was poured into a solution of potassium sodium tartrate (10percent w/v; 100 mL) and the resulting mixture was stirred at room temperature for 20 min.
The mixture was filtered through a pad of Celite, washing with ethyl acetate.
The organic layer of the filtrate was separated and the aqueous layer was extracted with ethyl acetate (2*100 mL).
The combined organic layers were dried (magnesium sulfate), filtered and eluted through a silica plug using 40percent ethyl acetate/hexanes to give (6-methoxy-pyridin-3-yl)-methanol (1.8 g, 72percent) as a clear oil.
51%
Stage #1: With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 2 h;
Stage #2: With sodium hydroxide; water In tetrahydrofuran at 0 - 20℃; for 0.5 h;
EXAMPLE B
(6-Methoxy-pyridin-3-yl)-methanol
To lithium aluminium hydride (0.68 g, 18 mmol) suspended in dry THF (10 ml) was added dropwise a solution of methyl 6-methoxynicotinate (1 g, 6 mmol) in dry THF (5 ml).
The reaction mixture was stirred for 2 h at r.t. then cooled (ice-bath) and quenched with water (2 ml) followed by the further addition of 1 N NaOH (6 ml) and water (2 ml).
The cold-bath was removed and the mixture stirred for 30 min at r.t., filtered and concentrated under reduced pressure.
The residue was diluted with water and extracted with ethyl acetate (3*).
The combined organic extracts were washed with water, brine, dried (MgSO4), filtered and concentrated under reduced pressure to give a crude oil which was purified over silica gel (ethyl acetate/n-heptane 1:1): colorless oil 0.45 g (51percent);
1H NMR (CDCl3) δ 1.69 (t, 1H), 3.94 (s, 3H), 4.62 (d, 2H), 6.75 (d, 1H), 7.62 (dd, 1H), 8.13 (d, 1H); MS: m/e=139.0(M+)
51% With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 2 h; EXAMPLE B
(6-Methoxy-pyridin-3-yl)-methanol
To lithium aluminium hydride (0.68 g, 18 mmol) suspended in dry THF (10 ml) was added dropwise a solution of methyl 6-methoxynicotinate (1 g, 6 mmol) in dry THF (5 ml).
The reaction mixture was stirred for 2 h at r.t. then cooled (ice-bath) and quenched with water (2 ml) followed by the further addition of 1N NaOH (6 ml) and water (2 ml).
The cold-bath was removed and the mixture stirred for 30 min at r.t., filtered and concentrated under reduced pressure.
The residue was diluted with water and extracted with ethyl acetate (3*).
The combined organic extracts were washed with water, brine, dried (MgSO4), filtered and concentrated under reduced pressure to give a crude oil which was purified over silica gel (ethyl acetate/n-heptane 1:1): colorless oil 0.45 g (51percent);
1H NMR (CDCl3) δ 1.69 (t, 1H), 3.94 (s, 3H), 4.62 (d, 2H), 6.75 (d, 1H), 7.62 (dd, 1H), 8.13 (d, 1H); MS: m/e=139.0 (M+)
35% With sodium tetrahydroborate In 1,4-dioxane at 0 - 100℃; A solution of methyl 2-methoxypyridine-5-carboxylate (8.4 g, 50 mmol) in dixoane (70 mL) was treated with sodium borohydride (8.1 g, 244 mmol) at 0 °C. The reaction mixture was warmed to 100 °C and heating continued overnight. After this time, the mixture was cooled, diluted with methanol, filtered through a fritted funnel with methanol washes, and the filtrate was concentrated. The residue was redissolved in water, 0.5 M sodium hydroxide was added dropwise, and the mixture extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, dichloromethane/methanol) to afford the title compound (2.9 g, 35percent) as a colorless oil. MW = 139.15. ]H NMR (CD3OD, 300 MHz) δ 8.11-8.05 (m, 1H), 7.67 (dd, Jl = 10.9 Hz, J2 = 2.43 Hz, 1H), 6.77 (d, J = 8.5 Hz, 1H), 4.89 (s, 1H), 4.54 (s, 2H), 3.89 (s, 3H); APCI MS m/z 140 [M + H]+.

Reference: [1] Patent: US2006/235225, 2006, A1, . Location in patent: Page/Page column 3
[2] Patent: WO2011/73845, 2011, A1, . Location in patent: Page/Page column 123
[3] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 5, p. 1644 - 1658
[4] Patent: WO2015/158427, 2015, A1, . Location in patent: Page/Page column 132
[5] Tetrahedron, 1992, vol. 48, # 8, p. 1457 - 1464
[6] Tetrahedron, 2014, vol. 70, # 40, p. 7207 - 7220
[7] Patent: US2007/49632, 2007, A1, . Location in patent: Page/Page column 38
[8] Journal of Labelled Compounds and Radiopharmaceuticals, 2007, vol. 50, # 5-6, p. 613 - 615
[9] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 1, p. 304 - 308
[10] Patent: US2007/37789, 2007, A1, . Location in patent: Page/Page column 10
[11] Patent: US2006/14945, 2006, A1, . Location in patent: Page/Page column 39
[12] Patent: WO2014/66659, 2014, A1, . Location in patent: Paragraph 0808
[13] Patent: WO2007/75567, 2007, A1, . Location in patent: Page/Page column 91-92
[14] Patent: EP2060572, 2009, A1, . Location in patent: Page/Page column 36-37
[15] Patent: EP2058310, 2009, A1, . Location in patent: Page/Page column 50
[16] Patent: US2010/179321, 2010, A1, . Location in patent: Page/Page column 3-4
[17] Patent: EP1621537, 2006, A1, . Location in patent: Page/Page column 35
[18] Organic Letters, 2010, vol. 12, # 21, p. 5004 - 5007
[19] Patent: US2011/224225, 2011, A1, . Location in patent: Page/Page column 23
[20] Journal of Organic Chemistry, 2011, vol. 76, # 20, p. 8336 - 8346
[21] Patent: WO2011/159554, 2011, A1, . Location in patent: Page/Page column 31-32
[22] Patent: WO2011/159553, 2011, A1, . Location in patent: Page/Page column 27-28
[23] Patent: WO2011/84368, 2011, A1, . Location in patent: Page/Page column 54-55
[24] Organic Letters, 2017, vol. 19, # 14, p. 3895 - 3898
  • 6
  • [ 26218-80-4 ]
  • [ 101990-70-9 ]
Reference: [1] Patent: US2011/224225, 2011, A1,
[2] Journal of Organic Chemistry, 2011, vol. 76, # 20, p. 8336 - 8346
[3] Patent: WO2011/159554, 2011, A1,
[4] Patent: WO2011/159553, 2011, A1,
[5] Patent: WO2011/84368, 2011, A1,
[6] Organic Letters, 2017, vol. 19, # 14, p. 3895 - 3898
[7] Tetrahedron, 2014, vol. 70, # 40, p. 7207 - 7220
  • 7
  • [ 26218-80-4 ]
  • [ 213193-32-9 ]
Reference: [1] Tetrahedron, 2014, vol. 70, # 40, p. 7207 - 7220
  • 8
  • [ 26218-80-4 ]
  • [ 128632-03-1 ]
Reference: [1] Journal of Labelled Compounds and Radiopharmaceuticals, 2007, vol. 50, # 5-6, p. 613 - 615
[2] Patent: US2004/121316, 2004, A1,
Historical Records

Related Functional Groups of
[ 26218-80-4 ]

Esters

Chemical Structure| 66171-50-4

[ 66171-50-4 ]

Methyl 6-hydroxynicotinate

Similarity: 0.98

Chemical Structure| 93-60-7

[ 93-60-7 ]

3-(Methoxycarbonyl)pyridine

Similarity: 0.88

Chemical Structure| 59237-50-2

[ 59237-50-2 ]

Methyl 5-amino-6-methoxynicotinate

Similarity: 0.87

Chemical Structure| 79398-27-9

[ 79398-27-9 ]

Methyl 4,6-dihydroxynicotinate

Similarity: 0.86

Chemical Structure| 129747-52-0

[ 129747-52-0 ]

Methyl 5-(hydroxymethyl)nicotinate

Similarity: 0.85

Ethers

Chemical Structure| 66572-55-2

[ 66572-55-2 ]

2-Methoxy-5-pyridinecarboxylic acid

Similarity: 0.97

Chemical Structure| 223127-05-7

[ 223127-05-7 ]

6-Isopropoxynicotinic acid

Similarity: 0.92

Chemical Structure| 635712-99-1

[ 635712-99-1 ]

6-(Benzyloxy)nicotinaldehyde

Similarity: 0.88

Chemical Structure| 59237-50-2

[ 59237-50-2 ]

Methyl 5-amino-6-methoxynicotinate

Similarity: 0.87

Chemical Structure| 65873-72-5

[ 65873-72-5 ]

6-Methoxynicotinaldehyde

Similarity: 0.86

Related Parent Nucleus of
[ 26218-80-4 ]

Pyridines

Chemical Structure| 66171-50-4

[ 66171-50-4 ]

Methyl 6-hydroxynicotinate

Similarity: 0.98

Chemical Structure| 66572-55-2

[ 66572-55-2 ]

2-Methoxy-5-pyridinecarboxylic acid

Similarity: 0.97

Chemical Structure| 223127-05-7

[ 223127-05-7 ]

6-Isopropoxynicotinic acid

Similarity: 0.92

Chemical Structure| 635712-99-1

[ 635712-99-1 ]

6-(Benzyloxy)nicotinaldehyde

Similarity: 0.88

Chemical Structure| 93-60-7

[ 93-60-7 ]

3-(Methoxycarbonyl)pyridine

Similarity: 0.88