| 78% |
Stage #1: tert-butyl N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]carbamate With oxalyl dichloride; (methylsulfinyl)methane In dichloromethane at -60℃; for 0.5h;
Stage #2: With triethylamine In dichloromethane at -60℃; for 0.5h; |
|
| 68% |
With Dess-Martin periodane In dichloromethane at 0 - 25℃; for 16h; |
21 Synthesis of tert-butyl N-[3-formylbicyclo[1.1.1]pentan-1-yl]carbamate:
Into a 1000 mL 3-necked round-botom flask, were placed dichoromethane (300 mL), tert-butyl N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan- 1-yl]carbamate (4.0 g, 187.6 mmol, 1.0 eq). After that, Dess-martin periodinane (9.5 g, 225.1 mmol, 1.2 eq) was added in several batches at 0°C. The reaction mixture was stirred for 16 hours at 25°C. The resulting mixture was then quenched by the addition of water (300 mL), and then extracted with dichloromethane (3x400 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The crude residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether= 1 :1 to give of tert-butyl N-[3-formylbicyclo[1 .1 .1 ]pentan-1 -yl]carbamate (3.0 g, 68%) as a white solid. 1HNMR (400 MHz, DMSO-cfc) 5 9.60 (s, 1 H), 7.53 (d, J=72.0 Hz, 1 H), 2.11 (d, J=15.0 Hz, 5H), 2.05-1.67 (m, 1 H), 1.38 (s, 9H). |
| 68% |
With Dess-Martin periodane In dichloromethane at 0 - 25℃; for 16h; |
21 Synthesis of tert-butyl N-[3-formylbicyclo[1.1.1]pentan-1-yl]carbamate:
Into a 1000 mL 3-necked round-botom flask, were placed dichoromethane (300 mL), tert-butyl N-[3-(hydroxymethyl)bicyclo[1.1.1]pentan- 1-yl]carbamate (4.0 g, 187.6 mmol, 1.0 eq). After that, Dess-martin periodinane (9.5 g, 225.1 mmol, 1.2 eq) was added in several batches at 0°C. The reaction mixture was stirred for 16 hours at 25°C. The resulting mixture was then quenched by the addition of water (300 mL), and then extracted with dichloromethane (3x400 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The crude residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether= 1 :1 to give of tert-butyl N-[3-formylbicyclo[1 .1 .1 ]pentan-1 -yl]carbamate (3.0 g, 68%) as a white solid. 1HNMR (400 MHz, DMSO-cfc) 5 9.60 (s, 1 H), 7.53 (d, J=72.0 Hz, 1 H), 2.11 (d, J=15.0 Hz, 5H), 2.05-1.67 (m, 1 H), 1.38 (s, 9H). |
| 42.4% |
With Dess-Martin periodane In dichloromethane at 25℃; for 16h; |
7 Synthesis of tert-butyl N-[3-formylbicyclo[1.1.1]pentan-1-yl]carbamate.
Into a 50-mL, round-bottomed flask was placed DCM (10.00 mL), tert-butyl N-[3- (hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]carbamate (300.00 mg, 1.407 mmol, 1.00 equiv). This was followed by the addition of Dess-Martin Reagent (715.93 mg, 1.688 mmol, 1.20 equiv) in several batches. The resulting solution was stirred for 16 hr at 25 °C. The reaction was then quenched by the addition of 50 mL of water. The resulting solution was extracted with 3x30 mL of dichloromethane and the organic layers were combined and dried over anhydrous sodium sulfate and concentrated. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:1). The collected fractions were combined and concentrated. This resulted in 140 mg (42.40%) of tert-butyl N-[3-formylbicyclo[1.1.1]pentan-1-yl]carbamate as a white solid. |
| 42.4% |
With Dess-Martin periodane In dichloromethane at 25℃; for 16h; |
7 Synthesis of tert-butyl N-[3-formylbicyclo[1.1.1]pentan-1-yl]carbamate.
Into a 50-mL, round-bottomed flask was placed DCM (10.00 mL), tert-butyl N-[3- (hydroxymethyl)bicyclo[1.1.1]pentan-1-yl]carbamate (300.00 mg, 1.407 mmol, 1.00 equiv). This was followed by the addition of Dess-Martin Reagent (715.93 mg, 1.688 mmol, 1.20 equiv) in several batches. The resulting solution was stirred for 16 hr at 25 °C. The reaction was then quenched by the addition of 50 mL of water. The resulting solution was extracted with 3x30 mL of dichloromethane and the organic layers were combined and dried over anhydrous sodium sulfate and concentrated. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:1). The collected fractions were combined and concentrated. This resulted in 140 mg (42.40%) of tert-butyl N-[3-formylbicyclo[1.1.1]pentan-1-yl]carbamate as a white solid. |
|
With Sodium hydrogenocarbonate; Dess-Martin periodane In dichloromethane at 20℃; for 1.5h; |
14.1; 15.1 Example 15: cis-3 -(3 -methyl -3 -(1 -(4-(trifluoromethyl)benzyl)- 1H-indole-7-carboxamido) cyclobutyl)propanoic acid
Step 1: tert-butyl (3-formylbicyclo[1.1. 1]pentan-1-yl)carbamate: tert-butyl (3- (hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)carbamate (1 eq., Intermediate amine 1, Step 2) and sodium bicarbonate (1.5 eq.) were suspended in DCM (0.034 M). Dess-Martin periodinane (1.2 eq.) was added to the reaction mixture and stirred at RT for 1.5 h. The reaction mixture was then diluted with TBME and washed sequentially with 10% aq. Na2S2O3, 1 N aq. NaOH, water and brine. The organic extract was then dried over MgSO4 and filtered. Concentration of the filtrate in vacuo furnished the desired crude product as a white crystalline solid (68% yield). |
| 0.050 g |
With Dess-Martin periodane In dichloromethane at 20℃; for 0.5h; |
3 Procedure:
To a stirred solution of tert-butyl (3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)carbamate (INX-SM-3-2) (0.1 g, 0.48 mmol) in DCM (2 mL), Dess-Martin periodinane(DMP) (0.40 g, 40.93 mmol) was added at room temperature and stirred for 30 min. After completion of reaction as indicated by TLC, reaction mixture was quenched with saturated NaHCOs solution and extracted with ethyl acetate. The combined organic layer was dried over Na2S04and evaporated under vacuum to give crude product. The crude was purified by silica gel column chromatography (ethyl acetate/ hexane: 40:60) to give the title compound as white solid (0.050 g, 52 %).1H NMR (DMSO-d6) 6: 9.59(s, 1H), 7.68(bs, 1 H), 2.12(s, 6H), 1.37(s,9H). |
| 0.050 g |
With Dess-Martin periodane In dichloromethane at 20℃; for 0.5h; |
3 Procedure:
To a stirred solution of tert-butyl (3-(hydroxymethyl)bicyclo[1.1.1]pentan-1-yl)carbamate (INX-SM-3-2) (0.1 g, 0.48 mmol) in DCM (2 mL), Dess-Martin periodinane(DMP) (0.40 g, 40.93 mmol) was added at room temperature and stirred for 30 min. After completion of reaction as indicated by TLC, reaction mixture was quenched with saturated NaHCOs solution and extracted with ethyl acetate. The combined organic layer was dried over Na2S04and evaporated under vacuum to give crude product. The crude was purified by silica gel column chromatography (ethyl acetate/ hexane: 40:60) to give the title compound as white solid (0.050 g, 52 %).1H NMR (DMSO-d6) 6: 9.59(s, 1H), 7.68(bs, 1 H), 2.12(s, 6H), 1.37(s,9H). |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
