Hydrochloric Acid → HCID 11717794, compound

HRID 1813928Notes

Reaction equation

HRID 1813928 reaction equation
[CH2:1]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:12][N:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[C:22]([O:26][CH2:27][CH3:28])(=[O:25])[CH:23]=[CH2:24]>CCOC(C)=O>[CH2:1]([O:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12][N:11]1[CH2:24][CH2:23][C:22]([O:26][CH2:27][CH3:28])=[O:25])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8821Ethyl AcrylateHCID 10989367Ethyl 2-Benzyloxymethyl-5-pyridinecarboxylate

Product 1

HCID 11717794HCID 11717794, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To an EtOAc solution (0.9 mL) of 14c (271 mg, 1.0 mmol) was added 2 M ethereal HCl (3.6 mL), and then the solvent was removed in vacuo and the residual 14c.HCl salt was dissolved in MeOH (5.4 mL) and PtO2 (14 mg) was added. The mixture was hydrogenated under 1 atm of H2 (1 h). The catalyst was filtered, and the solvent was removed in vacuo. The residue was dissolved in aqueous 1 N NaOH (3.5 mL) and extracted with EtOAc (3×15 mL). The organic extracts were combined, dried (Na2SO4), concentrated, and then dissolved in ethyl acrylate (1.1 mL, 10 mmol) and stirred at 80° C. (20 h). The reaction was concentrated to dryness and the residue was separated by PTLC (EtOAc/hexanes=2/3) to give 15c (48 mg, 13%) and 17 (32 mg, 12%), respectively. Compound 15c: clear oil; Rf 0.57 (EtOAc/hexanes=1/1); IR (neat) 2978, 2935, 2862, 1731, 1454, 1372, 1181 cm−1; 1H NMR (CDCl3) δ 1.24 (t, J=7.2 Hz, 3H), 1.25 (t, J=7.2 Hz, 3H), 1.64-1.77 (m, 4H), 2.43-2.54 (m, 3H), 2.66 (dd, J=3.9, 12.2 Hz, 1H), 2.82-2.97 (m, 4H), 3.45 (dd, J=5.9, 9.6 Hz, 1H), 3.66 (dd, J=5.4, 9.6 Hz, 1H), 4.12 (q, J=7.2 Hz, 4H), 4.47 (1/2 AB, J=12.2 Hz, 1H), 4.52 (1/2 AB, J=12.2 Hz, 1H), 7.27-7.34 (m, 5H), 13C NMR (CDCl3) 14.1, 14.2, 23.3, 25.9, 33.1, 40.6, 50.1, 50.3, 57.6, 60.1, 60.2, 69.3, 73.2, 127.4, 127.5 (2C), 128.3 (2C), 138.3, 172.7, 174.1 ppm; MS (+CI) 378 [M+1]+; Mr (+CI) 378.228 63 [M+1]+ (calcd for C21H32NO5 378.228 05). Compound 17 (King et al., “Substituted Benzamides with Conformationally Restricted Side Chains. 5. Azabicyclo[xyz] Derivatives as 5-HT4 Receptor Agonists and Gastric Motility Stimulants”, J. Med. Chem. 1993, 36, 683-689) (cis- and trans-mixture): yellow oil; Rf 0.44 (EtOAc/hexanes=1/1); IR (neat) 2974, 2924, 2814, 1735, 1455, 1377 cm−1; 1H NMR (CDCl3) δ 1.00 (d, J=6.6 Hz, 1.4H), 1.10 (d, J=6.6 Hz, 1.6H), 1.23-1.28 (m, 6H), 1.40-2.01 (m, 4H), 2.18-2.31 (m, 1H), 2.42-2.59 (m, 4H), 2.67-2.88 (m, 2H), 3.03-3.10 (m, 1H), 4.08-4.17 (m, 4H), 13C NMR (CDCl3) 13.7 (2C), 14.2 (2C), 19.9 (2C), 23.1 (2C), 27.4 (2C), 32.7, 33.8, 41.2, 42.2, 48.8, 49.6, 49.8, 53.3, 54.1, 55.1, 60.2 (2C), 60.3 (2C), 172.8 (2C), 174.1 (2C) ppm; MS (+CI) 272 [M+1]+; Mr (+CI) 272.186 63 [M+1]+ (calcd for C14H26NO4 272.186 18).

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionHCl salt was dissolved in MeOH (5.4 mL)
  3. additionPtO2 (14 mg) was added
  4. customwas hydrogenated under 1 atm of H2 (1 h)
  5. filtrationThe catalyst was filtered
  6. customthe solvent was removed in vacuo
  7. dissolutionThe residue was dissolved in aqueous 1 N NaOH (3.5 mL)
  8. extractionextracted with EtOAc (3×15 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. concentrationThe reaction was concentrated to dryness
  12. customthe residue was separated by PTLC (EtOAc/hexanes=2/3)

Sources & evidence

ORD record
ord-13bb5bf7f5c74a50a6036fa427c69711
Source dataset
uspto-grants-2005_04
Patent number
US06875774B2

Reaction notes

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