Triethylamine → 1,1-Dimethylethyl 4-[4-[[methyl[(1R)-1-phenylpropyl]amino]carbonyl]-2-thiazolyl]-1-piperidinecarboxylate

1-(1,1-Dimethylethyl) 4-(4-carboxy-2-thiazolyl)-1-piperidinecarboxylate (i.e. the product of Example 1, Step B) (3.1 g, 9.9 mmol) was suspended in 10 mL of dry acetonitrile and treated with triethylamine (3.0 mL, 21 mmol) to give a homogeneous solution. To this was added O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (3.98 g, 10.5 mmol) followed by (α,R)-α-ethyl-N-methylbenzenemethanamine (i.e. the product of Example 1, Step C) (10 mmol, 1.50 g). The mixture was stirred at ambient temperature for 4 days, concentrated under reduced pressure, diluted with ethyl acetate, washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine, dried over MgSO4 and concentrated under reduced pressure to give 5.1 g of a dark oil. Purification by silica gel chromatography using 25% ethyl acetate in hexanes gave 3.6 g of the title compound as a yellow oil.

1. customto give a homogeneous solution
2. concentrationconcentrated under reduced pressure
3. additiondiluted with ethyl acetate
4. washwashed with 1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated under reduced pressure

ORD-Eintrag

ord-828105e7a65a46d88e01fe571fbf0f69

Quelldatensatz

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08586611B2