Lithium hydroxide, monohydrate → HCID 59997305, compound

Participants

Reaction Steps

To an ice cold solution of Ethyl (4-{(2S,3R)-2-({[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl}amino)-4-[(1,3-benzodioxol-5-ylsulfonyl)(isobutyl)amino]-3-hydroxybutyl}phenoxy)acetate (107 mg, 0.16 mmol) in tetrahydrofuran/water (4 mL, 3:1) was added lithium hydroxide monohydrate (21 mg, 0.48 mmol). The reaction was allowed to warm to ambient temperature and stir for 1 h. The tetrahydrofuran was evaporated and the residue diluted with water (30 mL). The aqueous was then extracted with ether (30 mL), cooled in an ice bath and acidified to pH ˜2 with 1.0 N hydrochloric acid. The resulting precipitate was extracted into ethyl acetate (30 mL), washed with water (20 mL), dried (magnesium sulfate) and concentrated in vacuo to a white solid. Triturated with 10% ether in hexane and filtered to afford the title compound (77 mg) as a 2:1 mixture with the compound derived from the loss of the bis-tetrahydrofuran alcohol and subsequent ring closure at the 2-hydroxy position. The mixture was confirmed by NMR, HPLC and mass spectra. Data for major product: 1H NMR (DMSO-d6): δ 0.78 (6H, dd), 1.17-1.45 (2H, m), 1.92 (1H, m), 2.35 (1H, t), 2.64-2.78 (3H, m), 2.88-3.02 (2H, m), 3.24-3.30 (1H, m), 3.40-3.60 (4H, m), 3.70 (1H, t), 3.78-3.82 (1H, m), 4.54 (2H, s), 4.82 (1H, q), 5.00 (1H, d), 5.46 (1H, d), 6.12 (2H, s), 6.71 (2H, d), 7.00-7.30 (6H, m), 12.85 (1H, broad); MS: 651 (MH+); C30H38N2O12S (by-product MS: 521 (MH+); C24H28N2O9S).

Provenance & Evidence