Methanol → (3S,4R)-3-Hydroxymethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of (3S*,4R*)-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (1.29 g, 2.54 mmol) (Example 1 G) in THF (25 mL), a solution of borane dimethylsulfide complex (2M in THF, 2.80 mL, 5.58 mmol) is slowly added at −10° C. The mixture is stirred for 20 min at −10° C., then allowed to reach RT and further stirred overnight. MeOH is carefully added (exothermic!), and the mixture is concentrated under reduced pressure. MeOH is again added, and the mixture is concentrated. This operation is repeated 3 times, and the mixture is finally taken up into a saturated aqueous solution of NaHCO3 and extracted 3 times with CH2Cl2. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH from 100:0 to 95:5) to give the desired product. TLC, Rf (CH2Cl2/MeOH 95:5)=0.3. MS (LC-MS): 395.1 [M+H-Boc]+; tR (HPLC, C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 5.01 min.

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