4-(3-chlorophenyl)-tetrahydro-2H-pyran-4-carbonitrile synthesis

Yield:-

Reaction Conditions:

Stage #1: 3-chloro-benzeneacetonitrilewith potassium tert-butylate in N,N-dimethyl-formamide at 0; for 0.166667 h;
Stage #2: 3-oxa-1,5-dichloropentane in N,N-dimethyl-formamide at 0 - 20; for 20 h;

Steps:

46.A

Step A: Preparation of 4-(3-Chlorophenyl)-tetrahydro-2H-pyran-4-carbonitrile; [0589] Potassium tert-butoxide (8.90 g, 79.3 mmol, 2.20 eq) was added to a stirred solution of 2-(3-chlorophenyl)acetonitrile (4.26 mL, 36.1 mmol) in DMF (50 mL) at 0⁰C under a nitrogen atmosphere. The mixture was stirred for 10 minutes at O⁰C before l-chloro-2-(2-chloroethoxy)ethane (4.65 mL, 39.7 mmol) was added dropwise via syringe. The reaction mixture was allowed to warm to room temperature and stirred for 20 hours. The reaction mixture was then cooled to 0⁰C and quenched with 10% HCl. The aqueous mixture was extracted with EtOAc (2x). The combined organic layers were washed with brine, dried (MgSO₄), and concentrated in vacuo to give the product as an orange oil (12.51 g).

References:

WO2008/76427,2008,A2 Location in patent:Page/Page column 137-138