Pyrrolidine → HCID 68540432, compound

HRID 1992988Notes

Reaction equation

HRID 1992988 reaction equation
[CH3:1][C:2]1[C:3]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:4]([O:14][C:15]2[CH:20]=[CH:19][C:18](/[CH:21]=[CH:22]/[C:23]([OH:25])=O)=[CH:17][CH:16]=2)[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][CH:6]=2.C(Cl)(=O)C(Cl)=O.[NH:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1>C(Cl)Cl>[CH3:1][C:2]1[C:3]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:4]([O:14][C:15]2[CH:16]=[CH:17][C:18](/[CH:21]=[CH:22]/[C:23]([N:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)=[O:25])=[CH:19][CH:20]=2)[C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([O:12][CH3:13])=[CH:7][CH:6]=2

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 65578Oxalyl chlorideHCID 68534631HCID 68534631, compound

Product 1

HCID 68540432HCID 68540432, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2E)-3-(4-{[3-methyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}phenyl)-2-propenoic acid (10) (0.135 g, 0.33 mmol) in CH2Cl2 (2 mL) was added oxalyl chloride (0.043 mL, 0.49 mmol) under N2. The resultant mixture was stirred at room temperature for 2 h. Reaction mixture was concentrated under reduced pressure to afford the crude acid chloride. The acid chloride was dried (Na2SO4) and re-dissolved in CH2Cl2 (5 mL) at room temperature. To the above solution pyrrolidine (0.055 ml, 0.66 mmol) was introduced slowly and the mixture was stirred for 12 h. Reaction mixture was concentrated under reduced pressure to afford the crude amide. The product was purified by SiO2 column chromatography using hexanes:EtOAc (9:1 to 3:2) as an eluent to afford 0.146 g (96%) of the title compound (243) as a white foam. 1H NMR (400 MHz, CDCl3): δ 7.71 (d, J=9.2 Hz, 1H), 7.55 (s, 1H), 7.54 d, J=15.6 Hz, 1H), 7.27-7.20 (m, 5H), 7.13-7.11 (m, 3H), 7.03 and 7.01 (dd, J1=9.2 Hz, J2=2.4 Hz, 1H), 6.57 (d, J=8.8 Hz, 2H), 6.51 (d, J=15.2 Hz, 1H), 3.91 (s, 3H), 3.55 (t, J=6.8 Hz, 4H), 2.22 (s, 3H), 1.94 (quintet, J=6.4 Hz, 2H), 1.85 (quintet, J=6.8 Hz, 2H), 2.26 (s, 3H). LCMS (ESI) m/z 464.15 (M+H)+.

Workup

  1. customReaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. customto afford the crude acid chloride
  4. dry with materialThe acid chloride was dried (Na2SO4)
  5. dissolutionre-dissolved in CH2Cl2 (5 mL) at room temperature
  6. customReaction mixture
  7. concentrationwas concentrated under reduced pressure
  8. customto afford the crude amide
  9. customThe product was purified by SiO2 column chromatography

Sources & evidence

ORD record
ord-635059c16c7b41c1bb4c2ebbb71ce1c7
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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