Hydrochloric Acid → HCID 18963926, compound

HRID 257055Notes

Reaction equation

HRID 257055 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:20][CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:21][CH2:22][CH2:23][N:24]([C:26]([NH2:28])=[O:27])[OH:25])[CH:17]=3)[C:12]2=[O:29])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:37](Cl)(=[O:39])[CH3:38].Cl>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:20][CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:21][CH2:22][CH2:23][N:24]([C:26]([NH2:28])=[O:27])[O:25][C:37](=[O:39])[CH3:38])[CH:17]=3)[C:12]2=[O:29])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 9822360HCID 9822360, compound

Product 1

HCID 18963926HCID 18963926, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-[3-(4-fluorophenyl)-propyl]-6-[2-(N-aminocarbonyl-N-hydroxyamino)-ethoxy]-1-oxo-1,2,3,4-tetrahydroisoquinoline (500 mg, 1.2 mmol) and triethylamine (0.2 mL, 1.4 mmol) are dissolved in THF (25 mL) and acetyl chloride (0.1 mL, 1.4 mmol) is added. The reaction mixture is stirred for 2 hours and subsequently poured into 2N HCl. The aqueous phase is extracted with EtOAc (3×100 mL) and the combined organics washed with 2N HCl (2×100 mL) H2O (2×100 mL), saturated NaHCO3 solution (2×100 mL), saturated NaCl solution (2×100 mL), dried over MgSO4 and concentrated in vacuo. The residue is triturated with hexanes and chromatographed (silica gel, 1:1 EtOAc/hexane). The resulting material is crystallized from cold CH2Cl2 /Et2O and dried in vacuo to give 2-[3-(4-fluorophenyl)-propyl]-6-{2-[N-(aminocarbonyl)-N-(acetyloxy)amino]-ethoxy}-1-oxo-1,2,3,4-tetrahydroisoquinoline, m.p. 113°-114°.

Workup

  1. extractionThe aqueous phase is extracted with EtOAc (3×100 mL)
  2. washthe combined organics washed with 2N HCl (2×100 mL) H2O (2×100 mL), saturated NaHCO3 solution (2×100 mL), saturated NaCl solution (2×100 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is triturated with hexanes
  6. customchromatographed (silica gel, 1:1 EtOAc/hexane)
  7. customThe resulting material is crystallized from cold CH2Cl2 /Et2O
  8. customdried in vacuo

Sources & evidence

ORD record
ord-c4d910fcd5d94e8f9f418612b5c30751
Source dataset
uspto-grants-1993_11
Patent number
US05260316

Reaction notes

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