3,5-Di-tert-butyl-4-hydroxybenzoic acid → HCID 19753187, compound

HRID 1165769Notes

Reaction equation

HRID 1165769 reaction equation
C(C1C=C(C=C(C(C)(C)C)C=1O)C(O)=O)(C)(C)C.C(N1C=CN=C1)(N1C=CN=C1)=O.O[C@@H:32]1[C@H:38](C2C=CC(OC)=CC=2)[S:37][C:36]2[C:47]3[C:52]([CH:53]=[CH:54][C:35]=2[N:34](CCN(C)C)[C:33]1=[O:60])=[CH:51][CH:50]=[CH:49][CH:48]=3>O1CCCC1>[S:37]1[CH:38]=[CH:32][C:33](=[O:60])[NH:34][C:35]2[CH:54]=[CH:53][C:52]3[C:47]([C:36]1=2)=[CH:48][CH:49]=[CH:50][CH:51]=3

Participants

5

Reactant 3

HCID 150073,5-Di-tert-butyl-4-hydroxybenzoic acidHCID 682631,1'-CarbonyldiimidazoleHCID 13823438HCID 13823438, compound

Product 1

HCID 19753187HCID 19753187, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1.35 g (0.00054 mol) of 3,5-di-tert.-butyl-4-hydroxybenzoic acid and 0.9 g (0.0054 mol) of 1,1'-carbonyldiimidazole in 20 ml of dry tetrahydrofuran was stirred at room temperature for 30 minutes. To the above mixture 1.3 g (0.00031 mol) of (±)-cis-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-5-[2-(dimethylamino)ethyl]naphtho[1,2-b][1,4]thiazepin-4(5H)-one was added and stirred at room temperature for 17 hours then at reflux for 7 hours. After cooling the solids were filtered and the filtrate was concentrated to dryness. The residue was partitioned between ethyl acetate and dilute ammonium hydroxide. The ethyl acetate solutions were washed with brine, dried (MgSO4) and the solvent was removed under reduced pressure. The residue was dissolved in acetonitrile and chromatographed on 45 g of silica gel. The column was eluted wtih 50 ml portions of acetonitrile. Fractions 10-20 were combined and the solvent was removed to give 0.9 g of crude product, which was crystallized from ether to give 0.8 g (40%) of (±)-cis-2,3-dihydro-3-[[4-hydroxy-3,5-bis(1,1-dimethylethyl)benzoyl]oxy]-2-(4-methoxyphenyl)-5-[2-dimethylamino)ethyl]naphtho[1,2-b][1,4]thiazepin-4(5H)-one, mp 181°-182°.

Workup

  1. stirringstirred at room temperature for 17 hours
  2. temperatureat reflux for 7 hours
  3. temperatureAfter cooling the solids
  4. filtrationwere filtered
  5. concentrationthe filtrate was concentrated to dryness
  6. customThe residue was partitioned between ethyl acetate and dilute ammonium hydroxide
  7. washThe ethyl acetate solutions were washed with brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent was removed under reduced pressure
  10. dissolutionThe residue was dissolved in acetonitrile
  11. customchromatographed on 45 g of silica gel
  12. washThe column was eluted wtih 50 ml portions of acetonitrile
  13. customthe solvent was removed
  14. customto give 0.9 g of crude product, which
  15. customwas crystallized from ether

Sources & evidence

ORD record
ord-4199bdb7bc6248c89ab58b9bfa836f71
Source dataset
uspto-grants-1990_03
Patent number
US04912102

Reaction notes

Loading…