Acetic Acid → HCID 131727254, compound

HRID 1455324Notes

Reaction equation

HRID 1455324 reaction equation
[C:1]1([N:7]([CH2:28][CH2:29][CH3:30])[C@H:8]([C:13]([NH:15][N:16]=[CH:17][CH2:18][CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BH3-]C#N.[Na+].C(O)(=O)C>C1COCC1>[C:1]1([N:7]([CH2:28][CH2:29][CH3:30])[C@H:8]([C:13]([NH:15][NH:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 131727255HCID 131727255, compound

Product 1

HCID 131727254HCID 131727254, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

This procedure is based on the method used by Gallina et al. to synthesize a series of Z-hydrazines [Calbretta et al, Eur. J. Med. Chem. 30, 931 -941 (1995); incorporated herein by reference]. PhPr-Leu-NH—N═CH(CH2)2—NH-Boc (1.928 g, 4.46 mmol) and NaBH3CN (5 eq, 1.400 g, 22.3 mmol) were dissolved in anhydrous THF (23 mL). Glacial acetic acid (104 eq, 27.85 g, 464 mmol, 26.5 mL) was added dropwise to the solution, and the reaction mixture was allowed to stir at rt overnight. The solvents were evaporated and the crude oil dissolved in ethyl acetate (20 mL). Distilled water (20 mL) was added to the solution, which was vigorously stirred while enough solid NaHCO3 was added to turn the pH of the aqueous layer basic. The organic layer was isolated and washed with a saturated NaCl solution (2×15 mL), a saturated NaHCO3 solution (10 mL), and again with a saturated NaCl solution (10 mL). The organic layer was dried over MgSO4, filtered, and evaporated. The crude solid was purified by silica gel chromatography using 1/1 ethyl acetate/hexanes as the eluent. The solvent was evaporated, leaving a white, foamy solid that was used without further purification: yield 59%; product spot on TLC, Rf=0.43 (10% CH3OH in CH2Cl2). 1H NMR (CDCl3) δ 9.80 (s, 1H), 9.54 (s, 1H), 7.30-7.13 (m, 5H), 6.94 (s, 1H), 6.60 (s, 1H), 4.60-4.47 (m, 1H), 3.25-3.06 (m, 2H), 3.04-2.93 (m, 4H), 2.60-2.51 (m, 2H), 2.87-1.72 (m, 3H), 1.70-1.60 (m, 2H), 1.42 (s, 9H), 0.98-0.82 (m, 6H). MS (ESI+) m/z 435 (M+1).

Workup

  1. customThe solvents were evaporated
  2. dissolutionthe crude oil dissolved in ethyl acetate (20 mL)
  3. additionDistilled water (20 mL) was added to the solution, which
  4. stirringwas vigorously stirred while enough solid NaHCO3
  5. additionwas added
  6. customThe organic layer was isolated
  7. washwashed with a saturated NaCl solution (2×15 mL)
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude solid was purified by silica gel chromatography
  12. customThe solvent was evaporated
  13. customleaving a white, foamy solid that
  14. customwas used without further purification

Sources & evidence

ORD record
ord-cbd5c987d1bd45aaaa2bc485e95c94ed
Source dataset
uspto-grants-2009_01
Patent number
US07482379B2

Reaction notes

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