With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.33420-52-9, name is 2,2-Difluoropropan-1-ol, molecular formula is C3H6F2O, molecular weight is 96.076, as common compound, the synthetic route is as follows.Product Details of 33420-52-9
Trifluoromethanesulfonic anhydride (9.34 mL, 55.2 mmol) was added to a solution of 2,2-difluoropropan-1-ol (5.05 g, 52.6 mmol) in DCM (100 mL) at -10 C followed by dropwiseaddition of 2,6-dimethylpyridine (7.35 mL, 63.1 mmol) in DCM (50 mL). The reaction was stirred for 1 hour before addition of 2N HC1 (150 mL). The layers were separated and the aqueous phase was extracted with DCM (100 mL), then the combined organics were dried and concentrated carefully (no lower than 200 mbar, 40 C) to afford 2,2-difluoropropyltrifluoromethanesulfonate (12.90 g) as a brownlred oil that was used directly in next stage.2,2-Difluoropropyl trifluoromethanesulfonate (11.91 g, 52.22 mmol) was added to a solution of (R)-1-(1H-indol-3-yl)propan-2-amine (6.50 g, 37.3 mmol) and DIPEA (12.9 ml, 74.6 mmol) in 1 ,4-dioxane (75 mL) and the reaction was then heated to 65 C for 1.5 hours. The reaction was cooled to room temperature and diluted with EtOAc (250 mL). This waswashed with water (2 x 100 mL) and saturated aqueous sodium chloride (100 mL). The organic phase was separated and dried (MgSO4), filtered and evaporated. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM to afford (R)-N-( 1 -(1 H-indol-3 -yl)propan-2-yl)-2,2-difluoropropan- 1-amine (7.99 g, 85%) as an orange/brown oil. ?H NMR (500 MHz, CDC13, 27 C) 1.11 (3H, d), 1.58 (3H, t), 2.77 -3.00 (4H, m), 3.07 (1H, h), 7.04 (1H, d), 7.12 (1H, ddd), 7.19 (1H, ddd), 7.36 (1H, dt), 7.57- 7.62 (1H, m), 8.03 (1H, s). (One proton not observed). m/z: ES+ [M+H]+ 253.
At the same time, in my other blogs, there are other synthetic methods of this type of compound,33420-52-9, 2,2-Difluoropropan-1-ol, and friends who are interested can also refer to it.
Reference:
Patent; ASTRAZENECA AB; SCOTT, James, Stewart; MOSS, Thomas, Andrew; YANG, Bin; VARNES, Jeffrey, Gilbert; O’DONOVAN, Daniel, Hillebrand; NISSINK, Johannes, Wilhelmus, Maria; HUGHES, Samantha, Jayne; BARLAAM, Bernard, Christophe; WU, Dedong; BROO, Dan, Anders; (224 pag.)WO2018/19793; (2018); A1;,
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