Hydrochloric Acid → HCID 86607483, compound

HRID 1669982Notes

Reaction equation

HRID 1669982 reaction equation
[S:1](=[C:4]1[N:9]([C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[O:11])[CH2:8][CH2:7][NH:6][C@@H:5]1[C:18]([O-:20])=O)(=[O:3])=[O:2].[NH2:21]O.Cl>CN(C=O)C>[S:1](=[C:4]1[N:9]([C:10]([N:12]2[CH2:13][CH2:14][O:15][CH2:16][CH2:17]2)=[O:11])[CH2:8][CH2:7][NH:6][C@@H:5]1[C:18]([NH2:21])=[O:20])(=[O:2])=[O:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 86607484HCID 86607484, compound

Product 1

HCID 86607483HCID 86607483, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Step 5—Formation of N-hydroxy-1-[4-(4-fluorophenoxy) phenyl)]sulfonyl-4-(4-morpholinylcarbonyl)piperazine-2-(R)-carbox-amide Methyl 1-[4-(4-fluorophenoxy)phenyl)]sulfonyl-4-(4-morpholinylcarbonyl)piperazine-2-(R)-carboxylate (1.11 g, 2.2 mmol) was dissolved in DMF (17 mls) to which was added 50% aqueous NH2OH (20 mls) and the reaction mixture stirred at room temperature overnight. The reaction mixture was poured into cold 1.0N HCl (100-120 mls) and extracted with EtOAc (4×). The combined EtOAc extractions were washed with 10% aqueous LiCl (4×), saturated NaCl (1×), dried (Na2SO4), and concentrated in vacuo. The crude product was purified by flash chromatography (EtOAc) and the resulting pure oil was dissolved in 1:1 acetonitrile:water and lyophilized to give N-hydroxy-1-[4-(4-fluorophenoxy)phenyl)]sulfonyl-4-(4-morpholinylcarbonyl)piperazine-2-(R)-carboxamide as a white solid (659 mg, 59%). LC/MS Calcd for [M+H]+ 509.1. found 509.1. 1HNMR (400 MHz, CD3OD): δ 7.69 (d, 2H, J=9.2 Hz), 7.04 (m, 4H), 6.95 (d, 2H, J=9.2 Hz), 4.30 (m, 1H), 3.76 (m, 1H), 3.50 (m, 7H), 3.10 (m, 4H), 2.90 (dd, 1H, J=13.2, 4.4 Hz), 2.72 (m, 1H).

Workup

  1. extractionextracted with EtOAc (4×)
  2. extractionThe combined EtOAc extractions
  3. washwere washed with 10% aqueous LiCl (4×), saturated NaCl (1×)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography (EtOAc)
  7. dissolutionthe resulting pure oil was dissolved in 1:1 acetonitrile

Sources & evidence

ORD record
ord-697f0b68f5dd488c96fc4c18a95f0c36
Source dataset
uspto-grants-2011_08
Patent number
US07989661B2

Reaction notes

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