Lithium hydroxide, monohydrate → HCID 53812573, compound

HRID 588912Notes

Reaction equation

HRID 588912 reaction equation
C[O:2][C:3](=[O:21])[C:4]([CH3:20])([CH3:19])[NH:5][C:6](=[O:18])[C:7]([CH3:17])([CH3:16])[NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].O[Li].O>C1COCC1.O>[C:12]([O:11][C:9]([NH:8][C:7]([CH3:17])([CH3:16])[C:6]([NH:5][C:4]([CH3:20])([CH3:19])[C:3]([OH:21])=[O:2])=[O:18])=[O:10])([CH3:15])([CH3:13])[CH3:14]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 14805857HCID 14805857, compound

Product 1

HCID 53812573HCID 53812573, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-tert-butoxycarbonyl α,α-dimethylglycyl α,α-dimethylglycine methyl ester 3 (20.42 g, 67.53 mmol) was dissolved in THF (530 mL) and a solution of LiOH.H2O (8.50 g, 0.203 mol) in de-ionized H2O (270 mL) added in one portion. The reaction mixture was stirred for 4 h 30 min at room temperature. The solvents were evaporated and the residue redissolved in H2O (800 mL). The solution was washed with Et2O (2×500 mL) and acidified to pH 1-2 by addition of concentrated hydrochloric acid. This resulted in the precipitation of a white solid, which was collected by filtration, washed with H2O (4×100 mL) and dried under vacuum overnight (16.18 g, 83%). The compound has been prepared before,4 but as far as we have been able to establish has not been appropriately characterised; 1H NMR (200 MHz, DMSO-d6) δ 12.33 (br s, 1H, COOH), 7.43 (s, 1H, NH(Aib2)), 6.84 (br s, 1H, NH(Aib1)), 1.36 (s, 15H, (CH3)3/CH3), 1.27 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-d6) δ 175.9, 173.7, 154.2, 78.2, 55.8, 55.1, 28.1, 25.0, 24.4; HRMS (m/z): [M+Na]+ calcd. for C13H24N2O5Na, 311.1582. found, 311.1590; Anal. Calcd. for C13H24N2O5: C, 54.15; H, 8.39; N, 9.72. Found: C, 54.5; H, 8.4; N, 9.6.

Workup

  1. customThe solvents were evaporated
  2. dissolutionthe residue redissolved in H2O (800 mL)
  3. washThe solution was washed with Et2O (2×500 mL)
  4. additionacidified to pH 1-2 by addition of concentrated hydrochloric acid
  5. customThis resulted in the precipitation of a white solid, which
  6. filtrationwas collected by filtration
  7. washwashed with H2O (4×100 mL)
  8. customdried under vacuum overnight (16.18 g, 83%)
  9. customThe compound has been prepared before,4

Sources & evidence

ORD record
ord-db0a0ca621ac4dd29a5c7474a7e850ce
Source dataset
uspto-grants-2016_01
Patent number
US09227995B2

Reaction notes

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