Acetic Acid → 2-(4-((2S)-2-((di-3-oxetanylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

To a solution of 2-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.380 g, 0.845 mmol, Example 192, Step 1) in CH2Cl2 (8.0 mL) was added 3-oxetanone (0.20 mL, 2.5 mmol, Aldrich, St. Louis, Mo.), 4 molecular sieves (75 mg), acetic acid (0.015 mL, 0.17 mmol) and sodium triacetoxyborohydride (0.717 g, 3.38 mmol). The resulting mixture was stirred at room temperature for 15 h. The reaction mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and CH2Cl2 (40 mL). The aqueous layer was extracted with CH2Cl2 (2×15 mL) and the combined organic extracts were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (80 g of silica gel, 2 to 5% MeOH in CH2Cl2) to afford 2-(4-((2S)-2-((di-3-oxetanylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.116 g) as a mixture of two isomers:

1. customThe reaction mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and CH2Cl2 (40 mL)
2. extractionThe aqueous layer was extracted with CH2Cl2 (2×15 mL)
3. dry with materialthe combined organic extracts were dried over MgSO4
4. concentrationconcentrated
5. customThe crude product was purified by column chromatography (80 g of silica gel, 2 to 5% MeOH in CH2Cl2)

ORD record

ord-8deb4e6c6c0f43d6b04816936ba548ed

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431563B2