Lithium hydroxide, monohydrate → HCID 59709821, compound

HRID 2237371Notes

Reaction equation

HRID 2237371 reaction equation
C[O:2][C:3](=[O:27])[C@H:4]([CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[NH:5][C:6](=[O:21])[C@@H:7]([CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18])[NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].O.[OH-].[Li+]>O1CCCC1.O>[C:12]([O:11][C:9]([NH:8][C@@H:7]([C:6]([NH:5][C@H:4]([C:3]([OH:27])=[O:2])[CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:10])([CH3:13])([CH3:14])[CH3:15]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59302410HCID 59302410, compound

Product 1

HCID 59709821HCID 59709821, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

N-(tert-Butoxycarbonyl)-3-tert-butyl-D-alanyl-3-tert-butyl-L-alanine methyl ester (Example 8A, 36 g, 93.1 mmol) is dissolved in tetrahydrofuran p.a. (279 ml). At about 10° C., a solution of lithium hydroxide monohydrate (7.82 g, 186.3 mmol, 2 equivalents) in water (187 ml) is slowly added dropwise. When the HPLC chromatogram (Method 2) shows complete conversion (about 20 h), the reaction mixture is freed of the THF at 200 mbar and then extracted with methyl tert-butyl ether (200 ml). The organic phase is diluted with ethyl acetate (500 ml) and then water is added and the mixture is subsequently adjusted cautiously to pH 3-4 with 1 N aqueous hydrochloric acid. The combined organic phases are washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, evaporated in vacuo and dried under high vacuum. 97.4 g (97% of theory) of the title compound are added.

Workup

  1. customconversion (about 20 h)
  2. extractionextracted with methyl tert-butyl ether (200 ml)
  3. additionThe organic phase is diluted with ethyl acetate (500 ml)
  4. additionwater is added
  5. washThe combined organic phases are washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customdried under high vacuum
  10. addition97.4 g (97% of theory) of the title compound are added

Sources & evidence

ORD record
ord-c6b38fbbfc994339b8646d565fa3dfba
Source dataset
uspto-grants-2010_05
Patent number
US07718611B2

Reaction notes

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