Acetic Acid → HCID 58857938, compound

HRID 1162823Notes

Reaction equation

HRID 1162823 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, 22.1 mmol) in anhydrous THF (13.5 mL) was treated with triethylamine (3.03 mL, 21.6 mmol), 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, 24.1 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 and the mixture 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 title compound as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.19 (br s, 2H), 7.02-6.98 (m, 2H), 4.56-4.37 (m, 2H), 3.72 (s, 3H), 3.49 (s, 3H), 3.39 (br s, 2H), 3.05 (br s, 1H), 2.97 (br s, 1H), 2.66 (br s, 2H), 2.55 (s, 3H), 1.68-158 (m, 4H), 1.47 (br s, 9H). ES MS (M+1)=428.4.

Workup

  1. stirringthe mixture was 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-cd39e6a98ba04e17a31ba70863e66866
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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