hydroxylamine-O-sulfonic acid → HCID 23433523, compound

HRID 1280001Notes

Reaction equation

HRID 1280001 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3[S:19][C:20]([CH:23]=O)=[CH:21][CH:22]=3)=[CH:15][CH:16]=2)[C:11]([CH3:25])=[CH:10][C:9]1([CH3:27])[CH3:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:28]OS(O)(=O)=O>C(#N)C.O>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3[S:19][C:20]([C:23]#[N:28])=[CH:21][CH:22]=3)=[CH:15][CH:16]=2)[C:11]([CH3:25])=[CH:10][C:9]1([CH3:27])[CH3:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 76284hydroxylamine-O-sulfonic acidHCID 23433457HCID 23433457, compound

Product 1

HCID 23433523HCID 23433523, compoundYield 43.8%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
65 °C

Procedure

To a solution of 1-tert-butyloxycarbonyl-6-(5-formyl-2-thienyl)-1,2-dihydro-2,2,4-trimethylquinoline (12 mg, 0.03 mmol) in acetonitrile/water (10 ml/0.5 ml) was added hydroxylamine-O-sulphonic acid (5 mg, 0.04 mmol). The reaction mixture was heated to 65° C. for 1 h. The reaction was quenched with 10% NaOH (5 mL) and extracted with EtOAc (10 mL). The organic layer was washed with water and brine (3×5 mL each), dried (Na2SO4), and concentrated in vacuo to afford the crude product as a yellow oil. The crude product was purified by prep. TLC (20×20 cm, 250 μm, 25% EtOAc:hexane) to afford 5 mg (40%) of 1-tert-butyloxycarbonyl-6-(5-Cyano-2-thienyl)-1,2-dihydro-2,2,4-trimethylquinoline as a yellow oil. This product was dissolved in CH2Cl2 (5 mL) and treated with TFA (0.1 ml) at rt with stirring. After 2 h, the reaction was quenched with 10% NaOH (5 mL). The organic layer was washed with water and brine (3×5 mL each), dried (Na2SO4) and concentrated in vacuo to afford the crude product as a yellow oil. The crude product was purified by prep. TLC (20×20 cm, 250 μm, 25% EtOAc:hexane) to afford 2 mg (60%) of Compound 451 as a yellow oil. Data for Compound 451: Rf 0.3 (silica gel, 25% EtOAc:Hex); 1H NMR(400 MHz, CDCl3) 7.52 (d, J=4.0, 1H), 7.23 (s, 1H), 7.22 (d, J=7.4, 1H), 7.07 (d, J=4.0, 1H), 6.43 (d, J=7.4, 1H), 5.38 (s, 1H), 2.02 (s, 3H), 1.31 (s, 6H).

Workup

  1. customThe reaction was quenched with 10% NaOH (5 mL)
  2. extractionextracted with EtOAc (10 mL)
  3. washThe organic layer was washed with water and brine (3×5 mL each)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto afford the crude product as a yellow oil
  7. customThe crude product was purified by prep

Sources & evidence

ORD record
ord-13b0406fa9e14af38e6cf57a8b28574b
Source dataset
uspto-grants-2002_09
Patent number
US06448405B1

Reaction notes

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