Lithium hydroxide, monohydrate → HCID 59997305, compound

HRID 1815579Notes

Reaction equation

HRID 1815579 reaction equation
[O:1]1[C@H:5]2[O:6][CH2:7][CH2:8][C@H:4]2[C@@H:3]([O:9][C:10]([NH:12][C@H:13]([C@H:28]([OH:47])[CH2:29][N:30]([S:35]([C:38]2[CH:46]=[CH:45][C:41]3[O:42][CH2:43][O:44][C:40]=3[CH:39]=2)(=[O:37])=[O:36])[CH2:31][CH:32]([CH3:34])[CH3:33])[CH2:14][C:15]2[CH:27]=[CH:26][C:18]([O:19][CH2:20][C:21]([O:23]CC)=[O:22])=[CH:17][CH:16]=2)=[O:11])[CH2:2]1.O.[OH-].[Li+]>O1CCCC1.O>[O:1]1[C@H:5]2[O:6][CH2:7][CH2:8][C@H:4]2[C@@H:3]([O:9][C:10]([NH:12][C@H:13]([C@H:28]([OH:47])[CH2:29][N:30]([S:35]([C:38]2[CH:46]=[CH:45][C:41]3[O:42][CH2:43][O:44][C:40]=3[CH:39]=2)(=[O:37])=[O:36])[CH2:31][CH:32]([CH3:33])[CH3:34])[CH2:14][C:15]2[CH:27]=[CH:26][C:18]([O:19][CH2:20][C:21]([OH:23])=[O:22])=[CH:17][CH:16]=2)=[O:11])[CH2:2]1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59997210HCID 59997210, compound

Product 1

HCID 59997305HCID 59997305, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

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).

Workup

  1. customThe tetrahydrofuran was evaporated
  2. additionthe residue diluted with water (30 mL)
  3. extractionThe aqueous was then extracted with ether (30 mL)
  4. temperaturecooled in an ice bath
  5. extractionThe resulting precipitate was extracted into ethyl acetate (30 mL)
  6. washwashed with water (20 mL)
  7. dry with materialdried (magnesium sulfate)
  8. concentrationconcentrated in vacuo to a white solid
  9. customTriturated with 10% ether in hexane
  10. filtrationfiltered

Sources & evidence

ORD record
ord-b69a0c9c2b2a463f82e583b91b82a23d
Source dataset
uspto-grants-2005_04
Patent number
US06878728B1

Reaction notes

Loading…