Acetic Acid → HCID 25132791, compound

HRID 535957Notes

Reaction equation

HRID 535957 reaction equation
[CH3:1][C:2]([CH3:28])([CH3:27])[C@H:3]([NH:8][C:9]([C:11]1[N:12]=[C:13]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:14]2[CH2:20][CH2:19][CH2:18][NH:17][CH2:16][C:15]=12)=[O:10])[C:4]([NH:6][CH3:7])=[O:5].C=O.[C:31](O)(=O)C.[Na]>C1COCC1>[CH3:1][C:2]([CH3:28])([CH3:27])[C@H:3]([NH:8][C:9]([C:11]1[N:12]=[C:13]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:14]2[CH2:20][CH2:19][CH2:18][N:17]([CH3:31])[CH2:16][C:15]=12)=[O:10])[C:4]([NH:6][CH3:7])=[O:5]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5360545SodiumHCID 57635098HCID 57635098, compound

Product 1

HCID 25132791HCID 25132791, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Compound 314 (0.38 g), 30% aqueous paraformaldehyde (0.8 mL) and acetic acid (60 μL) in THF was added sodium triacetoxyboronhydride (0.42 g). After stirring at room temperature for two hours, the THF was removed by evaporation under reduced pressure. The residue was partitioned between saturated aqueous NaHCO3 and EtOAc. The organic phase was dried over anhydrous Na2SO4, filtered and evaporated to dryness. The residue was purified by column chromatography with 10% to 60% MeOH in DCM. The combined pure fractions were evaporated to give a white solid, which was triturated in EtOAc/DCM (2:1) and filtered. The filtrate was evaporated to dryness under reduced pressure. The resulting residue was extracted between water and DCM. The organic phase was dried over anhydrous Na2SO4 and evaporated to give Compound 317 (0.31 g). 1H-NMR (400 MHz, CDCl3) δ: 1.27 (s, 9H), 1.90 (br, 2H), 2.47 (s, 3H), 2.79 (d, J=4.8 Hz, 3H), 3.04 (br, 2H), 4.16 (br, 2H), 4.29 (d, J=9.5 Hz, 1H), 4.32 (br, 2H), 5.95 (br, 1H), 7.20-7.23 (dd, J=2.0, 9.6 Hz, 1H), 7.47-7.53 (m, 5H), 7.82 (d, J=9.5 Hz, 1H). LCMS (+ESI) m/z 398.2 [M+H]+.

Workup

  1. customthe THF was removed by evaporation under reduced pressure
  2. customThe residue was partitioned between saturated aqueous NaHCO3 and EtOAc
  3. dry with materialThe organic phase was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was purified by column chromatography with 10% to 60% MeOH in DCM
  7. customThe combined pure fractions were evaporated
  8. customto give a white solid, which
  9. customwas triturated in EtOAc/DCM (2:1)
  10. filtrationfiltered
  11. customThe filtrate was evaporated to dryness under reduced pressure
  12. extractionThe resulting residue was extracted between water and DCM
  13. dry with materialThe organic phase was dried over anhydrous Na2SO4
  14. customevaporated

Sources & evidence

ORD record
ord-45f2d7eb6aa34d97a76ec03d7210ffe7
Source dataset
uspto-grants-2014_10
Patent number
US08859538B2

Reaction notes

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