Acetic Acid → HCID 59468956, compound

Participants

Reaction Steps

The reaction was performed on the two separated batches of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-(2-oxoethyl)-1,2-pyrrolidinedicarboxylate obtained from the previous step (D37, Procedure 1). The first batch (109 g) was dissolved in MeOH (440 mL) and MeNH2 in MeOH 2M solution (347 mL) was added. AcOH (11 mL) was added. NaBH(OAc)3 (49 g) was added portion wise after 10 minutes. More NaBH(OAc)3 (14.7 g) was added portion wise at 25° C. The reaction mixture was quenched with 28% aqueous malic acid (200 mL) followed by AcOEt (1000 mL). K2CO3 was added up to pH˜9. Organic phase was concentrated to dryness, re-dissolved in EtOAc (500 mL) and extracted with 20% citric acid (4×300 mL). The combined aqueous phases were treated with EtOAc (500 mL) and solid K2CO3 was added until pH˜9. The phases were separated and the organic phase was dried under Na2SO4 and evaporated to dryness to afford the title compound (80 g). The second batch (180 g) was dissolved in MeOH (628 mL) and MeNH2 in MeOH 2M solution (300 mL) was added. AcOH (31 mL) was added. NaBH(OAc)3 (78.8 g) was added portionwise at 0° C. after 10 minutes. The reaction mixture was quenched with saturated NH4Cl (890 mL) and EtOAc (890 mL). The phases were separated and the aqueous was extracted with EtOAc (4×300 mL). The organic phase was dried over Na2SO4, concentrated to dryness, re-dissolved in EtOAc (500 mL) and extracted with 20% citric acid (6×150 mL). The combined aqueous phases were treated with EtOAc (600 mL) and solid K2CO3 was added until pH 8/9. The Phases were separated and the organic phase dried over Na2SO4 and evaporated to dryness to afford the title compound (78 g). 1H NMR (400 MHz, DMSO-d6) δ(ppm): 7.55 (m, 1H); 7.42 (m, 3H); 7.25 (m, 2H); 6.98 (m, 2H); 5.14 (m, 2H); 4.85-4.69 (2m, 1H); 3.75-3.73 (2s, 3H); 2.36 (bs, 3H) 2.80-2.25 (m, 2H); 2.20-2.00 (m, 3H); 1.70 (m, 1H); 1.32-1.00 (2s, 9H).

Provenance & Evidence