Acetic Acid → HCID 58857938, compound

HRID 2114825Notes

Reaction equation

HRID 2114825 reaction equation
[CH3:1][O:2][C:3](=[O:6])[CH2:4][NH2:5].C(N(CC)CC)C.[F:14][C:15]1[CH:38]=[CH:37][C:18]([CH2:19][N:20]([CH2:28][C:29](=O)[CH2:30][CH2:31][N:32]([O:34][CH3:35])[CH3:33])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:17][CH:16]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C([O-])(O)=O.[Na+]>C1COCC1>[C:23]([O:22][C:21]([N:20]([CH2:28][CH:29]([NH:5][CH2:4][C:3]([O:2][CH3:1])=[O:6])[CH2:30][CH2:31][N:32]([O:34][CH3:35])[CH3:33])[CH2:19][C:18]1[CH:17]=[CH:16][C:15]([F:14])=[CH:38][CH:37]=1)=[O:27])([CH3:26])([CH3:25])[CH3:24]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 8471TriethylamineHCID 69221Glycine methyl esterHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 58857940HCID 58857940, compound

Product 1

HCID 58857938HCID 58857938, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of glycine methyl ester (2.78 g, 22.14 mmol) in anhydrous THF (13.5 mL) was treated sequentially with triethylamine (3.03 mL, 21.55 mmol), a solution of tert-butyl 4-fluorobenzyl{4-[methoxy(methyl)amino]-2-oxobutyl}carbamate (1.50 g, 4.23 mmol) in anhydrous THF (8.5 mL), sodium triacetoxyborohydride (5.11 g, 24.11 mmol), and acetic acid (485 μL, 8.46 mmol). The mixture was stirred at ambient temperature under inert atmosphere for 42 h. Saturated aqueous NaHCO3 solution was added to the reaction which was stirred until gas evolution ceased. The mixture was extracted into EtOAc, and the aqueous layer was saturated with NaCl and extracted into EtOAc again. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to a pale yellow oil. Purification by silica gel chromatography using gradient elution (hexanes to 40% EtOAc/hexanes to EtOAc) afforded the amine as a colorless oil.

Workup

  1. stirringwas stirred until gas evolution
  2. extractionThe mixture was extracted into EtOAc
  3. extractionextracted into EtOAc again
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo to a pale yellow oil
  7. customPurification by silica gel chromatography
  8. washelution (hexanes to 40% EtOAc/hexanes to EtOAc)

Sources & evidence

ORD record
ord-bde8a1bdfabb43e68f2bf60078469579
Source dataset
uspto-grants-2008_10
Patent number
US07435735B2

Reaction notes

Loading…