Structure of 91182-60-4
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CAS No. : | 91182-60-4 |
Formula : | C11H8BrNO3 |
M.W : | 282.09 |
SMILES Code : | O=C(C1=C(C2=CC=C(Br)C=C2)ON=C1C)O |
MDL No. : | MFCD16447083 |
InChI Key : | GFLKZFOUAHOGJF-UHFFFAOYSA-N |
Pubchem ID : | 56604559 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 11 |
Fraction Csp3 | 0.09 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 61.56 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.33 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.03 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.65 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.11 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.92 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.54 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.64 |
Solubility | 0.0653 mg/ml ; 0.000232 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.63 |
Solubility | 0.066 mg/ml ; 0.000234 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.37 |
Solubility | 0.0122 mg/ml ; 0.0000432 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
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 |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.14 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.8 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | To a stirred solution of ester (3.2 g, 0.010M) in THF/H2O (79/35 ml) was added lithium hydroxide (2.4 g, 0.010M). The reaction mixture was stirred at room temperature for over night and the solvent, THF was removed from the reaction mixture under vacuum. The resulting mass was diluted with water and washed with diethyl ether (2×50 ml). Then the aqueous solution was acidified with sat. Oxalic acid (PH4) and was extracted with ethyl acetate (2×75 ml). The combined organic layer was dried over anhydrous sodium sulphate, concentrated under vacuum to give the pure product 2.8 g (96%). 1H NMR (DMSO-d6): delta 2.52 (3H, s), 7.37 (2H, dd), 7.91 (2H, dd), 12.42 (1H, br s). 13C NMR (DMSO-d6) delta 12.0, 110.0, 126.6, 127.2, 131.7, 132.5, 162.4, 164.4, 172.7. MH+=282. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 80℃; | Step 1: 5-(4'-Ethoxycarbonylmethyl-biphenyl-4-yl)-3-methyl-isoxazole-4-carboxylic acid5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (2.0 g, 7.07 mmol), [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (2.46 g, 8.5 mmol), tetrakis(triphenylphosphine)palladium(0) (0.80 g, 0.70 mmol), and sodium bicarbonate (4.3 g, 52 mmol) were combined in 1,4-dioxane (50 mL) and water (10 mL), and the reaction was stirred overnight at 80 C. to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | To a stirred solution of I-5a (0.66 g, 2.23 mmol) in 10 mL of MeOH/H20 (v/v=5: l) was added lithium hydroxide (0.12 g, 2.74 mmol). The solution was heated to reflux under nitrogen for 1 hr. MeOH was removed in vacuo and the residue was adjusted to pH = 2. The aqueous phase was extracted with DCM (50 mLX3). The combined organic layer was washed with brine, dried over Na2S04, concentrated to afford compound 1-4 (0.36 g, yield 58%). MS (ESI) m/z (M+H)+ 280. | |
Step 4: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid; [00441] 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid methyl ester (7.5g, 25mmol) was suspended in 2:1 methanol: water. Lithium hydroxide (2.1g, 50mmol) was added, and the reaction was stirred overnight at room temperature. The mixture was acidified to pH 1 with IN aqueous HCl and extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound. | ||
Step 4: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acidLithium hydroxide (2 g, 48 mmol) was added to a solution of 5-(4-bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid methyl ester (39 mmol) in methanol (50 mL) and water (10 mL), and the reaction was stirred at 60 C. for 1 hour. Acidic work-up gave the title compound. |
Lithium hydroxide (2g, 47.7mmol) was added to a solution of 5-(4-bromo-phenyl)-3-methyl- isoxazole-4-carboxylic acid methyl ester (7g, 23.6mmol) in MeOH (5OmL) and H2O (1OmL), and the reaction was stirred at 6O0C for 1 hour. Acidic work-up the title compound. | ||
With water; lithium hydroxide; In methanol; at 60℃; for 1h; | Step 4: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid methyl ester (39 mmol) in MeOH (50 mL) and H2O (10 mL) was treated with lithium hydroxide (2 g, 48 mmol), and the reaction was stirred at 60 C. for 1 hour. The mixture was acidified, and standard workup provided the title compound. | |
Step 4: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid methyl ester (39 mmol) in MeOH (50 mL) and H2O (10 mL) was treated with lithium hydroxide (2 g, 48 mmol) and the reaction was stirred at 60 C. for 1 hour. The mixture was acidified, and standard workup provided the title compound. | ||
With water; lithium hydroxide; In methanol; at 60℃; for 1h; | [00478] Step 4: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid[00479] Lithium hydroxide (2g, 48mmol) was added to a solution of 5-(4-bromo-phenyl)-3-methyl- isoxazole-4-carboxylic acid methyl ester (39mmol) in methanol (50mL) and water (lOmL), and the reaction was stirred at 60C for 1 hour. Acidic work-up gave the title compound. | |
With water; lithium hydroxide; In methanol; at 60℃; for 1h; | [00501] Step 4: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid: Lithium hydroxide (2g, 47.7mmol) was added to a solution of 5-(4-bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid methyl ester (7g, 23.6mmol) in MeOH (50mL) and H20 (lOmL), and the reaction was stirred at 60C for 1 hour. Acidic work-up the title compound. | |
With water; lithium hydroxide; In methanol; at 60℃; for 1h; | Step 4: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid methyl ester (39 mmol) in MeOH (50 mL) and H2O (10 mL) was treated with lithium hydroxide (2 g, 48 mmol), and the reaction was stirred at 60 C. for 1 hour. The mixture was acidified, and standard workup provided the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With diphenyl phosphoryl azide; triethylamine; In toluene; at 80℃; for 2.5h; | Step 5: [5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid l-(2-chloro- phenyl)-ethyl ester[00442] To a suspension of <strong>[91182-60-4]5-(4-bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid</strong> (7.Og, 24.8mmol) and triethylamine (3.46g, 24.8mmol) in toluene (25OmL) was added diphenylphosphoryl azide (5.3ImL, 24.8mmol), followed by 2-chloro-alpha-methylbenzyl alcohol (3.88g, 24.8mmol), and the reaction was stirred at 8O0C for 2.5 hours. The mixture was partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated, and the residue was dissolved in EtOAc and filtered through Celite to remove a precipitate that was present. The crude material was purified by silica gel chromatography to give the title compound. | |
Step 1: To <strong>[91182-60-4]5-(4-bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid</strong> (5.764 g, 20.4 mmol) in toluene (200 mL) was added triethylamine (3.13 mL, 22.4 mmol) and diphenylphosphoryl azide (4.42 mL, 20.4 mmol), and the mixture was stirred for 5 minutes at room temperature. 2-Chloro-alpha-methylbenzyl alcohol (3.2 g, 22.4 mol) was added, and the reaction was stirred at 80 C. for 2 hours. The mixture was diluted with EtOAc (200 mL) and extracted with EtOAc. The combined organic layers were washed twice with water and once with brine, and the combined aqueous layers were back-extracted with EtOAc. The combined organic layers were concentrated, and the residue was purified by silica gel chromatography to give [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid 1-(2-chloro-phenyl)-ethyl ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With diphenyl phosphoryl azide; triethylamine; In toluene; at 80℃; for 3h; | To a solution of compound XLV-1 (8 g, 28.08 mmol) in dry toluene (150 mL) was added compound XLV-2 (1.58 g, 10.1 mmol), triethylamine (8.0 mL) and DPPA (9.2 g, 33.6 mmol). The reaction mixture was heated to 80 C for 3 hours. The mixture was diluted with EtOAc (50 mL), washed with brine, dried over Na2S04, filtered and concentrated. The residue was purified by column chromatography (PE/EA = 10 IX) to give compound XLV-3 (9.4 g, yield: 83 %). MS (ESI) m/z (M+H)+ 402.0. |
With diphenyl phosphoryl azide; triethylamine; In toluene; at 75℃; for 2h; | Step 2: [5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid (R)-1-phenyl-ethyl ester5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (25 g, 88.7 mmol) in toluene (500 mL) was added triethylamine (18.5 mL, 133 mmol), followed by diphenylphosphoryl azide (22.1 mL, 101.9 mmol). (R)-(+)-1-Phenylethyl alcohol (11.9 mL, 97.5 mmol) was added, and the reaction was stirred at 75 C. for 2 hours. The mixture was partitioned between EtOAc and H2O and filtered through Celite. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound. | |
With diphenyl phosphoryl azide; triethylamine; In toluene; at 80℃; for 4h; | 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (2.Og, 7.09mmol) and triethylamine (0.99mL, 7.09mmol) were dissolved in toluene (5OmL). Diphenylphosphoryl azide (1.5mL, 7.09mmol) was added, followed by (R)-(+)-l- phenylethyl alcohol (0.865g, 7.09mmol; commercially available or prepared using procedures desribed herein or in the literature: e.g. E.J. Corey et al. J. Am. Chem. 1987, 109, 5551-5553), and the reaction was stirred at 8O0C for 4 hours. The mixture was concentrated, and the residue was purified by silica gel chromatography to give the title compound. |
With diphenyl phosphoryl azide; triethylamine; In toluene; at 75℃; for 2h;Product distribution / selectivity; | Step 2: [5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid (R)-l-phenyl-ethyl ester[00483] 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (25g, 88.7mmol) in toluene (500mL) was added triethylamine (18.5mL, 133mmol), followed by diphenylphosphoryl azide (22.1mL, 101.9mmol). (R)-(+)- 1 -Phenylethyl alcohol (11.9mL, 97.5mmol) was added, and the reaction was stirred at 75C for 2 hours. The mixture was partitioned between EtOAc and H 0 and filtered through Celite. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgS04, filtered, and concentrated to give the title compound. | |
With diphenyl phosphoryl azide; triethylamine; In toluene; at 80℃; for 4h; | Step 5: [5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid (R)-l-phenyl-ethyl ester: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (2.0g, 7.09mmol) and triethylamine (0.99mL, 7.09mmol) were dissolved in toluene (50mL). Diphenylphosphoryl azide (1.5mL, 7.09mmol) was added, followed by (R)-(+)- 1 -phenylethyl alcohol (0.865g, 7.09mmol; commercially available or prepared using procedures desribed herein or in the literature: e.g. E.J. Corey et al. J. Am. Chem. 1987, 109, 5551-5553), and the reaction was stirred at 80C for 4 hours. The mixture was concentrated, and the residue was purified by silica gel chromatography to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With diphenyl phosphoryl azide; triethylamine; In toluene; at 90℃; for 3h; | A mixture of compound 1-3 (1.87 g, 12 mmol), compound 1-4 (2.82 g, 10 mmol), DPPA (3.3 g, 12 mmol) and TEA (2.02 g, 20 mmol) in toluene was stirred at 90C for 3 hrs. The mixture was diluted with EtOAc (100 mL), washed with water and brine. The organic layer was dried over Na2S04, filtered, and concentrated. The residue was purified by column chromatography on silica gel (Petroleum ether: EtOAc = 30:1) to afford 1-5 (3 g, yield 69%). |
With diphenyl phosphoryl azide; triethylamine; In toluene; at 90℃; for 1h; | Step 2: [5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid (R)-1-(2-chloro-phenyl)-ethyl ester5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (10 g, 35 mmol), (R)-1-(2-chloro-phenyl)-ethanol (6.6 g, 42 mmol), triethylamine (10 mL, 70 mmol), and diphenylphosphoryl azide (11.5 g, 42 mmol) were combined in toluene (100 mL) and stirred at 90 C. for 1 hour. The mixture was concentrated, and the residue was purified by silica gel chromatography (0-30% EtOAc in hexanes). The isolated product was recrystallized in 5:1 hexanes:acetone to give the title compound in >99% e.e (by chiral HPLC. Chiracel OD 98.4% hexanes/1.6% Ethanol. Major isomer 27.9 min minor isomer 32.7 min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (4 g, 14.2 mmol) was dissolved in toluene (150 mL). Triethylamine (2.187 mL, 15.6 mmol) was added, followed by diphenylphosphoryl azide (3.372 mL, 15.6 mmol), and the mixture was stirred for 10 minutes. 2-Fluoro-alpha-methylbenzyl alcohol (2 g, 15.6 mmol) was added, and the reaction was stirred at 80 C. overnight. The mixture was cooled to room temperature and concentrated, and the residue was partitioned between with EtOAc and water. The organic layer was washed 4 times with water and once with brine, and then dried, filtered, and concentrated, and the residue was purified by silica gel chromatography (dry load; 0-100% EtOAc in hexanes) to give [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid 1-(2-fluoro-phenyl)-ethyl ester. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 5: 5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-ylamine 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (1.1 g, 4.1 mmol), diphenylphosphoryl azide (1.2 mL, 4.3 mmol), and triethylamine (1.14 mL, 8.2 mmol) were combined in toluene and stirred at 120 C. for 25 minutes. After cooling to room temperature, H2O (2 mL) in THF (2 mL) was added and the reaction was stirred at 88 C. for 2 hours. The mixture was cooled to room temperature and extracted with EtOAc. The combined organic layers were concentrated to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With diphenyl phosphoryl azide; triethylamine; In toluene; at 90℃; for 3h; | Compound VII-1 (300 mg, 1.02 mmol) was dissolved in 15 mL of toluene. To the resulting solution was added DPPA (353 mg, 1.28 mmol), t-BuOH (95 mg, 1.28 mmol) and Et3N (216 mg, 2.14 mmol), and then the solution was stirred at 90 C for 3 hrs. After cooling to rt, the mixture was poured into water and extracted with EtOAc (30 mLx 3). The combined organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo. The residue was purified by prep-TLC (Petroleum ether:EtOAc = 3: 1) to afford compound VII-2 (250 mg, yield 66%). |
With diphenylphosphoranyl azide; triethylamine;Reflux; | Step 5 : [5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-yl[-carbamic acid tert-butyl ester : 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (1.6 g, 6.0 mmol), diphenylphosphoryl azide (1.6 g, 6.0 mmol), and triethylamine (1.3 mL, 9.3 mmol) were combined in t-BuOH and refluxed overnight. After cooling, the mixture was concentrated, and the residue was partitioned between EtOAc and H2O. The organic layer was separated and concentrated, and the residue was purified by silica gel chromatography (16-18% EtOAc in hexanes) to give the title compound. | |
With diphenyl phosphoryl azide; triethylamine;Reflux; | Step 5: [5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid tert-butyl ester 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (1.6 g, 6.0 mmol), diphenylphosphoryl azide (1.6 g, 6.0 mmol), and triethylamine (1.3 mL, 9.3 mmol) were combined in t-BuOH and refluxed overnight. After cooling, the mixture was concentrated, and the residue was partitioned between EtOAc and H2O. The organic layer was separated and concentrated, and the residue was purified by silica gel chromatography (16-18% EtOAc in hexanes) to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1: [5-(4-Bromo-phenyl)-3-methyl-isoxazol-4-yl]-(5-phenyl-[1,3,4]oxadiazol-2-yl)-amine 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (1 g, 3.6 mmol), triethylamine (1 mL, 7.2 mmol) and diphenylphosphoryl azide (1.98 g, 7.2 mmol) were placed in toluene (20 mL) and heated to 60 C. for 20 minutes. Benzoic acid hydrazide (0.98 g, 7.2 mmol) was added in a single portion and the reaction was heated and stirred for 2 hours. The reaction was cooled and submitted to aqueous workup. The crude material was dissolved in dioxane (100 mL), phosphorous(V) oxychloride was added and the reaction was heated to 100 C. overnight. The reaction was cooled and worked up and the residue was purified on silica gel (0-80% EtOAc in hexanes) to yield the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid hydrazide 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (0.061 g, 2.16 mmol) was dissolved in THF (5 mL) then 1,1'-carbonyldiimidazole (0.390 g, 2.38 mmol) was added and the reaction was heated to 70 C. for 40 minutes. The reaction was then cooled to 0 C. and hydrazine monohydrate (0.220 mL, 4.32 mmol) was added. The reaction was then allowed to slowly warm to room temperature and stirred overnight. Standard aqueous workup afforded the title compound, which was brought to the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 3h;Inert atmosphere; | Step 1: 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carbonyl chloride 5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (4.2 g, 14.89 mmol) was dissolved in CH2Cl2 (42 mL) under N2 atmosphere. Oxalyl chloride (2.6 mL, 29.78 mmol) and DMF (5 drops) were added and the reaction stirred for 2.5 hours at room temperature. Then, additional oxalyl chloride (5 mL, 57.3 mmol) was added. After 30 minutes, the reaction mixture was concentrated and placed under high vacuum. The crude material was used directly in the next step. |
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