Reaction #52955

ord-f99ab618a70f43b898de3389cea6b161

Reaction equation

COc1cc(CN2CCSCC2)cc(OC)c1B(O)O
2,6-dimethoxy-4-(thiomorpholinomethyl)-benzeneboronic acid
CCOC(=O)[C@H](Cc1ccc(Br)cc1)NC(=O)c1c(Cl)cccc1Cl
N-(2,6-dichlorobenzoyl)-4-bromo-L-phenylalanine ethyl ester
O=C([O-])[O-].[K+].[K+]
K2CO3
→
CCOC(=O)[C@H](Cc1ccc(-c2c(OC)cc(CN3CCSCC3)cc2OC)cc1)NC(=O)c1c(Cl)cccc1Cl
N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(thiomorpholinomethyl)phenyl]-L-phenylalanine ethyl ester
Yield 15.2%

Reactants

COc1cc(CN2CCSCC2)cc(OC)c1B(O)O
2,6-dimethoxy-4-(thiomorpholinomethyl)-benzeneboronic acid
CCOC(=O)[C@H](Cc1ccc(Br)cc1)NC(=O)c1c(Cl)cccc1Cl
N-(2,6-dichlorobenzoyl)-4-bromo-L-phenylalanine ethyl ester
O=C([O-])[O-].[K+].[K+]
K2CO3

Reagents

c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Pd(PPh3)4

Solvents

COCCOC.O
DME H2O

Conditions

Temperature
80°CELSIUS
Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Otherpurified

Procedure

A mixture of 2,6-dimethoxy-4-(thiomorpholinomethyl)-benzeneboronic acid (1.1 g), N-(2,6-dichlorobenzoyl)-4-bromo-L-phenylalanine ethyl ester (0.71 g), Pd(PPh3)4 (1.0 g) and K2CO3 (1.00 g) in DME/H2O (10 mL/0.5 mL) was heated at 80° C. for 6 h under N2. The mixture was worked up and purified according to the procedure described in Example 8-3) to yield 0.15 g of N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(thiomorpholinomethyl)phenyl]-L-phenylalanine ethyl ester. mp. 86-89° C. ESMS: m/z 616 (MH+). HCl salt: mp. 204-205° C.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US06855843B2uspto-grants-2005_02