Lithium hydroxide, monohydrate → HCID 53644547, compound

HRID 588915Notes

Reaction equation

HRID 588915 reaction equation
C[O:2][C:3](=[O:27])[C:4]([CH3:26])([CH3:25])[NH:5][C:6](=[O:24])[C:7]([CH3:23])([CH3:22])[NH:8][C:9](=[O:21])[C:10]([CH3:20])([CH3:19])[NH:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].O[Li].O>C1COCC1.O>[C:15]([O:14][C:12]([NH:11][C:10]([CH3:20])([CH3:19])[C:9]([NH:8][C:7]([CH3:23])([CH3:22])[C:6]([NH:5][C:4]([CH3:26])([CH3:25])[C:3]([OH:27])=[O:2])=[O:24])=[O:21])=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 87403496HCID 87403496, compound

Product 1

HCID 53644547HCID 53644547, compoundYield 89.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-tert-butoxycarbonyl α,α-dimethylglycyl α,α-dimethylglycyl α,α-dimethylglycine methyl ester 6 (2.14 g, 5.52 mmol) was dissolved in THF (60 mL) and a solution of LiOH.H2O (0.695 g, 16.6 mmol) in de-ionized H2O (30 mL) added. The reaction mixture was stirred for 3 h at room temperature before the bulk of solvent was evaporated and the solution diluted with H2O (100 mL). The solution was washed with Et2O (2×40 mL) and acidified to pH 2 by addition of 5 M HCl. A white solid precipitated and was collected by filtration. The residue was washed with icecold H2O (30 mL) and dried under high vacuum affording the title compound as a white solid (1.84 g, 89%). The compound has been prepared before,6 but as far as we have been able to establish has not been appropriately characterised; 1H NMR (200 MHz, DMSO-d6) δ 11.84 (br s, 1H, COOH), 7.59 (s, 1H, NH(Aib)), 7.48 (s, 1H, NH(Aib)), 7.18 (s, 1H, NH(Aib1)), 1.40 (s, 9H, (CH3)3), 1.32 (s, 6H, CH3), 1.28 (s, 6H, CH3), 1.25 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-d6) δ 175.5, 173.5, 173.4, 155.1, 78.7, 55.8, 55.5, 54.8, 28.1, 24.8, 24.7, 24.6; HRMS (m/z): [M+Na]+ calcd. for C17H31N3O6Na, 396.2110. found, 396.2115; Anal. Calcd. for C17H31N3O6: C, 54.68; H, 8.37; N, 11.25. Found: C, 55.0; H, 8.4; N, 11.1.

Workup

  1. customwas evaporated
  2. additionthe solution diluted with H2O (100 mL)
  3. washThe solution was washed with Et2O (2×40 mL)
  4. additionacidified to pH 2 by addition of 5 M HCl
  5. customA white solid precipitated
  6. filtrationwas collected by filtration
  7. washThe residue was washed with icecold H2O (30 mL)
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-bbd7e72dd0c24f229fe1486a4d08b96b
Source dataset
uspto-grants-2016_01
Patent number
US09227995B2

Reaction notes

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