HCID 89670264, compound → HCID 89653854, compound

HRID 537310Notes

Reaction equation

HRID 537310 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=O)[CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)=[C:4]([NH:21][CH2:22][CH:23]([CH3:25])[CH3:24])[CH:3]=1>CC(O)=O>[CH3:19][O:18][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[O:11][CH2:10][C:9]1[N:21]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:4]2[CH:3]=[C:2]([OH:1])[CH:7]=[CH:6][C:5]=2[N:8]=1

Participants

3

Reactant 1

HCID 89670264HCID 89670264, compound

Product 1

HCID 89653854HCID 89653854, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 65a (5.5 g, 0.016 mol) in AcOH (50 mL) was heated at 100° C. for 1 hr. The reaction mixture was then concentrated in vacuo. The residue was dissolved in CH2Cl2 (100 mL), washed with saturated NaHCO3 (2×75 mL) and brine (75 mL), filtered through phase separation filter paper, and concentrated in vacuo to give a solid. The solid was triturated with EtOAc (35 mL), collected, and dried to give 3.7 g (71%) of 66a. HPLC analysis showed a purity of 80%. The solid was chromatographed on 75 g silica gel with 25 g of anhydrous sodium sulfate on top packed with hexanes. The column was eluted with 50 mL portions of 10% EtOAc in hexanes for fractions 1-4, 25% EtOAc in hexanes for fractions 5-8, and 50% EtOAc in hexanes for fractions 9-28. The pure product was eluted in fractions 15-20 (HPLC analysis) to give 3.2 g (61%) of 66a as a white solid. HPLC analysis showed a purity of 97%. 1H NMR (60 MHz, CDCl3): δ 7.7 (d, 1H), 7.4-6.4 (m, 6H), 6.8 (br s, 1H), 5.0 (s, 2H), 4.1 (d, 2H), 3.7 (s, 3H), 2.5-1.6 (m, 1H), 1.0 (d, 6H) ppm.

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2 (100 mL)
  3. washwashed with saturated NaHCO3 (2×75 mL) and brine (75 mL)
  4. filtrationfiltered through phase separation
  5. filtrationfilter paper
  6. concentrationconcentrated in vacuo
  7. customto give a solid
  8. customThe solid was triturated with EtOAc (35 mL)
  9. customcollected
  10. customdried

Sources & evidence

ORD record
ord-e634dceb7f56462bbf4d95f5c625c6c4
Source dataset
uspto-grants-2014_10
Patent number
US08859780B2

Reaction notes

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