Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 135992966, compound

HRID 968825Notes

Reaction equation

HRID 968825 reaction equation
[CH2:1]([O:3][C:4]([C:6]([CH3:34])([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][C:18]([NH:20][N:21]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=2)[C:22]([NH2:24])=[O:23])=O)=[CH:11][CH:10]=1)[CH3:7])=[O:5])[CH3:2].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:5])[C:6]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][C:18]2[NH:24][C:22](=[O:23])[N:21]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=3)[N:20]=2)=[CH:11][CH:10]=1)([CH3:34])[CH3:7])[CH3:2]

Participants

4

Reactant 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 59015846HCID 59015846, compound

Product 1

HCID 135992966HCID 135992966, compoundYield 49.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

1-[4-[4-(1-Ethoxycarbonyl-1-methylethoxy)phenyl]butyryl]-2-(3-methoxyphenylmethyl)semicarbazide (4.08 g, 8.65 mmol) was dissolved in ethyl acetate (7.5 mL). 1S (+)-10-camphorsulfonic acid (2.21 g, 9.51 mmol) was added in one portion and the solution was heated to reflux overnight. The solution was cooled to rt and washed with sat'd aq. NaHCO3 (40 mL×2) followed by 1N HCl (40 mL×2). The organic was concentrated to an orange oil. This oil was redissolved in ethyl acetate (40 mL). Amberlyst-15 resin (4.41 g) was added and the mixture was heated to 50° C. and stirred for 4 hours to remove de-ureated impurity. The mixture was then cooled to ambient temperature, filtered, concentrated, and purified by column chromatography (SiO2, 9:1 ethyl acetate: hexanes) to afford the title compound as an orange oil (1.93 g, 49.2%). 1H NMR (DMSO-d6) δ 11.47 (s, 1 H), 7.22 (t, 1H, J=8 Hz), 7.04 (d, 2H, J=8 Hz), 6.82 (d, 1H, J=2 Hz), 6.76 (m, 2H), 6.68 (d, 2H, J=2 Hz), 4.73 (s, 2H), 4.13 (q, 2H, J=7 Hz), 3.69 (s, 3H), 2.48 (t, 2H, J=8 Hz), 2.36 (t, 2H, J=8 Hz), 1.80 (quint, 2 H, J=7 Hz), 1.47 (s, 6H), 1.14 (t, 3H, J=7 Hz); 13C NMR (DMSO-d6) δ 174.0, 160.0, 155.0, 153.8, 146.7, 139.8, 135.5, 130.2, 129.8, 120.1, 119.5, 113.8, 113.2, 79.2, 61.6, 55.6, 47.8, 34.0, 28.4, 26.2, 25.7, 14.6; IR (CHCl3) 2940, 1692, 1508, 1467 cm−1; Anal. Calcd. for C25H31N3O5: C, 66.21.; H, 6.89; N, 9.26. Found: C, 66.29; H, 6.75; N, 9.19.

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux overnight
  3. washwashed with sat'd aq. NaHCO3 (40 mL×2)
  4. concentrationThe organic was concentrated to an orange oil
  5. dissolutionThis oil was redissolved in ethyl acetate (40 mL)
  6. additionAmberlyst-15 resin (4.41 g) was added
  7. temperaturethe mixture was heated to 50° C.
  8. customto remove de-ureated impurity
  9. temperatureThe mixture was then cooled to ambient temperature
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custompurified by column chromatography (SiO2, 9:1 ethyl acetate: hexanes)

Sources & evidence

ORD record
ord-37d1f9b6e5ea4ceaa1ee40346c15711e
Source dataset
uspto-grants-2007_12
Patent number
US07304062B2

Reaction notes

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