Dicyclohexylcarbodiimide → (R)-((R)-quinuclidin-3-yl) 2-(tert-butoxycarbonylamino)-2-phenylacetate

A mixture of (R)-2-((tert-Butoxycarbonyl)amino)-2-phenylacetic acid (5.0 g, 19.9 mmol), (R) enantiomeric pure form commercially available or obtainable from I-41 with known methods e.g. chiral preparative SFC, (R)-quinuclidin-3-ol (3.8 g, 29.8 mmol), N,N′-Dicyclohexylcarbodiimide (4.72 g, 22.9 mmol) and 1-hydroxybenzotriazole hydrate (3.09 g, 22.9 mmol) in tetrahydrofuran (175 mL) was stirred at room temperature for 18 h. After this time the reaction mixture was filtered through a pad of Celite® and concentrated in vacuo. The residue was partitioned between ethyl acetate (100 mL) and 10% aqueous sodium carbonate solution (50 mL), and the organic fractions were dried over magnesium sulfate, filtered and the solvent was removed in vacuo. Trituration with cold methanol gave the title compound as a white solid (898 mg, 17%) as a single diastereoisomer.

1. filtrationAfter this time the reaction mixture was filtered through a pad of Celite®
2. concentrationconcentrated in vacuo
3. customThe residue was partitioned between ethyl acetate (100 mL) and 10% aqueous sodium carbonate solution (50 mL)
4. dry with materialthe organic fractions were dried over magnesium sulfate
5. filtrationfiltered
6. customthe solvent was removed in vacuo

ORD record

ord-aacf24cd20dd4b3aac892368da0ffcc1

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133185B2