Tetrahydrofuran → HCID 69733822, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 3,4-dihydro-6-[[(phenylmethoxy)carbonyl]amino]-2(1H)-isoquinolinecarboxylate (Step 2, 7.05 g, 16.93 mmol) in dry THF (85 mL) at −78° C. under N2 is treated with n-butyllithium (11.1 mL, 1.6M in hexanes, 17.77 mmol) dropwise over 10 mins. The resulting mixture is stirred at −78° C. for 45 mins and is then treated with (R)-(−)-glycidyl butyrate (2.52 mL, 17.77 mmol) dropwise. The resulting mixture is stirred at −78° C. for 30 mins and is then warmed to ambient temperature and stirred for an additional 20 hrs. The reaction is then quenched with saturated aqueous NH4Cl (25 mL), diluted with H2O (25 mL) and extracted with EtOAc (100 mL). The organic phase is washed with H2O (2×50 mL) and brine (25 mL), dried over anhydrous MgSO4 and concentrated under reduced pressure to give the crude product which is then chromatographed on silica gel (350 g, 230-400 mesh), eluting with a gradient of MeOH/CH2Cl2 (1/99-3/97). Pooling and concentration of those fractions with an Rf=0.29 by TLC (MeOH/CHCl3, 5/95) provides 4.48 g (69%) of the title compound as an amorphous, white solid. 1H NMR (400 MHz, CDCl3) δ 7.37 (m, 7H), 7.11 (m, 1H), 5.19 (s, 2H), 4.75 (m, 1H), 4.63 (s, 2H), 4.00 (m, 3H), 3.75 (m, 3H), 2.86 (m, 2H) 1.65 (bs, 1H); MS (ESI+) for C21H22N2O5 m/z 383 (M+H)+; [α]25D=16° (c 0.52, chloroform).

Provenance & Evidence