Potassium Carbonate → HCID 58459264, compound

HRID 2036567Notes

Reaction equation

HRID 2036567 reaction equation
[NH:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:2]([C:4](O)=O)[CH3:3].[NH2:14][C:15]1[CH:16]=[C:17]([F:22])[CH:18]=[CH:19][C:20]=1[NH2:21].C([O-])([O-])=O.[K+].[K+]>N1C=CC=CC=1.CCOC(C)=O.CC(O)=O>[F:22][C:17]1[CH:18]=[CH:19][C:20]2[N:21]=[C:4]([C@@H:2]([NH:1][C:7](=[O:8])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH3:3])[NH:14][C:15]=2[CH:16]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 85082Tert-butoxycarbonylalanineHCID 1645844-Fluorobenzene-1,2-diamine

Product 1

HCID 58459264HCID 58459264, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Boc-L-Ala-OH (3.00 g, 15.86 mmol) and 3,4-diamino-1-fluorobenzene (2.00 g, 15.86 mmol) were mixed in pyridine (52.9 mL). EDCBCl (9.12 g, 47.6 mmol) was added and the mixture was stirred at ambient temperature for 20 min. The reaction mixture was diluted with EtOAc, washed with water, 1.0 N HCl and brine. The organic layer was dried with Na2SO4, filtered, and concentrated. The crude residue was purified by column chromatography on a 120 g of Redi-Sep™ column using 0 to 100% gradient of EtOAc in hexane as eluent. The desired fractions were combined and concentrated under reduced pressure to give the crude amide intermediate. The amide was dissolved in AcOH (26.9 mL) and heated in an oil bath at 70° C. for about 30 min. The reaction mixture was diluted with EtOAc and carefully neutralized with aq. K2CO3. The organic layer was washed with NaCl, dried with Na2SO4, and filtered. The filtrate was concentrated to dryness to yield (S)-tert-butyl 1-(6-fluoro-1H-benzo[d]imidazol-2-yl)ethylcarbamate: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.23 (1H, br. s.), 7.15-7.61 (3H, m), 6.98 (1H, t, J=8.5 Hz), 4.78-4.89 (1H, m), 1.46 (3H, d, J=7.0 Hz), 1.40 (9H, s); LC-MS (ESI) m/z 280.1 [M+H]+.

Workup

  1. additionEDCBCl (9.12 g, 47.6 mmol) was added
  2. washwashed with water, 1.0 N HCl and brine
  3. dry with materialThe organic layer was dried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by column chromatography on a 120 g of Redi-Sep™ column
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude amide intermediate
  9. temperatureheated in an oil bath at 70° C. for about 30 min
  10. washThe organic layer was washed with NaCl
  11. dry with materialdried with Na2SO4
  12. filtrationfiltered
  13. concentrationThe filtrate was concentrated to dryness

Sources & evidence

ORD record
ord-99d820c867f447539be51f30db6bff71
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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