Sodium Hydroxide → HCID 58915962, compound

HRID 476401Notes

Reaction equation

HRID 476401 reaction equation
[CH2:1]([O:4][C:5]([N:7]1[C:13]2[CH:14]=[C:15]([O:20][CH2:21][CH2:22][CH2:23][C:24]([O:26]C)=[O:25])[C:16]([O:18][CH3:19])=[CH:17][C:12]=2[C:11](=[O:28])[N:10]2[CH2:29][CH2:30][CH2:31][C@H:9]2[CH:8]1[O:32][CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][O:34]1)=[O:6])[CH:2]=[CH2:3].[OH-].[Na+]>CO.O>[CH2:1]([O:4][C:5]([N:7]1[C:13]2[CH:14]=[C:15]([O:20][CH2:21][CH2:22][CH2:23][C:24]([OH:26])=[O:25])[C:16]([O:18][CH3:19])=[CH:17][C:12]=2[C:11](=[O:28])[N:10]2[CH2:29][CH2:30][CH2:31][C@H:9]2[CH:8]1[O:32][CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][O:34]1)=[O:6])[CH:2]=[CH2:3]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 68845327HCID 68845327, compound

Product 1

HCID 58915962HCID 58915962, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

The methyl ester 18 (2.2 g, 4.26 mmol) was dissolved in MeOH (30 mL). Sodium hydroxide (340 mg, 8.5 mmol) was dissolved in water (7 mL) and added to the ester solution. The reaction mixture was stirred at 70° C. for 15 min. The methanol was then removed under vacuum and water (20 mL) was added. The aqueous solution was allowed to return to room temperature and a 5% aqueous citric acid solution was added to adjust the pH to <4. The precipitate was extracted with EtOAc (100 mL). The organic layer was washed with brine (30 mL) and dried over MgSO4. The solvent was removed under vacuum, then diethylether (50 mL) was added to the residue and removed under vacuum, then dried under vacuum to yield the pure 19 as white foam 2.10 g (98%). 1H NMR (d6-DMSO) as a mixture of 4/5 of diastereoisomers δ 7.10 (2H, s×2), 6.90-6.84 (2H, s×2), 5.84-5.68 (4H, m), 5.45-4.91 (6H, m), 4.72-4.30 (4H, m), 4.09-3.93 (4H, m), 3.91-3.75 (8H, m), 3.60-3.44 (4H, m), 3.44-3.22 (8H, m), 2.46-2.33 (4H, m), 2.20-1.76 (14H, m), 1.76-1.31 (12H, m). 13C NMR (d6-DMSO) δ 173.9, 173.9, 171.9, 166.1, 166.0, 149.6, 148.4, 148.3, 132.6, 116.5, 114.4, 110.5, 110.3, 99.2, 67.5, 67.4, 65.6, 65.5, 62.8, 59.4, 55.7, 45.9, 30.5, 30.2, 29.8, 29.7, 28.4, 28.3, 24.9, 24.8, 23.9, 23.8, 22.9, 22.7; MS (ES+) m/z (relative intensity) 519.2 ([M+H]+, 100). This compound was proved optically pure at C11a by reesterification (EDCI, HOBt, then MeOH), THP removal (AcOH/THF/H2O) and chiral HPLC, as in Tercel et al., J. Med. Chem., 2003, 46, 2132-2151).

Workup

  1. customThe methanol was then removed under vacuum and water (20 mL)
  2. additionwas added
  3. customto return to room temperature
  4. additiona 5% aqueous citric acid solution was added
  5. extractionThe precipitate was extracted with EtOAc (100 mL)
  6. washThe organic layer was washed with brine (30 mL)
  7. dry with materialdried over MgSO4
  8. customThe solvent was removed under vacuum
  9. additiondiethylether (50 mL) was added to the residue
  10. customremoved under vacuum
  11. customdried under vacuum

Sources & evidence

ORD record
ord-bc376d5d56c34a5e9d755f80a3c4c2bf
Source dataset
uspto-grants-2014_01
Patent number
US08637664B2

Reaction notes

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