(3R)-3-methoxypyrrolidine

Conditions: temp:90.01; pressure:0.00; stir:

Procedure: A mixture of 3,5-dibromopyridine (0.644 g, 2.72 mmol), (R)-3-methoxypyrrolidine (0.25 g, 2.47 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (0.045 g, 0.05 mmol), sodium 2-methylpropan-2-olate (0.356 g, 3.71 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.077 g, 0.12 mmol) in degassed toluene (7.5 ml) was sealed into a microwave tube and stirred for 16 hours at 90 °C. The reaction was completed. After cooling, an aqueous solution of Na2CO3 was added. Extraction with DCM (twice). The organic layers were dried over MgSO4 and evaporated _in vacuo_ to give the crude product as an orange oil. PBO-04062-54-01 It was purified by chromatography (Merck cartridge SVF D26 - SI60 15-40 µm - 30 g) on silica gel eluting with EtOAc 0 to 25% in petroleum ether. Pure collected fractions were evaporated to afford (R)-3-bromo-5-(3-methoxypyrrolidin-1-yl)pyridine (0.325 g, 51.1 %) as a yellow oil. PBO-04062-54-02

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner analogous to the method described in examples 99, (1S,5R)-3-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-3-aza-bicyclo[3.1.0]hexane-6-carboxylic acid (prepared from the ethyl ester, example 135) was coupled with (R)-3-methoxy-pyrrolidine (Aldrich) to give the title compound. HR-MS (ES, m/z) calculated for C40H48Cl2N5O4 [(M+H)+] 708.3078, observed 708.3078.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner analogous to the method described in example 99, {4-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetic acid was coupled with (R)-3-methoxy-pyrrolidine (Aldrich) to give the title compound. HR-MS (ES, m/z) calculated for C40H51Cl2N6O4 [(M+H)+] 749.3344, observed 749.3337.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepare using the method of Intermediate 49 with p-toluenesulfonic acid monohydrate (0.207 g, 1.09 mmol), crude tert-butyl (3R)-3-methoxypyrrolidine-1-carboxylate and (3R)-3-methoxypyrrolidine (See Intermediate 58) (0.42 g, 1.09 mmol) and ethanol (2 mL) to give the title compound as a red solid (0.42 g): MS (m/e): 102(M+1). Prepare

Conditions: temp:90.01; pressure:0.00; stir: