O-(Tetrahydropyran-2-yl)hydroxylamine → HCID 87208915, compound

HRID 2046742Notes

Reaction equation

HRID 2046742 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][C:13]3([CH2:24][C:23](=[O:25])[C:22]4[C:17](=[CH:18][CH:19]=[C:20](/[CH:26]=[CH:27]/[C:28](O)=[O:29])[CH:21]=4)[O:16]3)[CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[NH2:31][O:32][CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][O:34]1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]2[CH2:11][CH2:12][C:13]3([CH2:24][C:23](=[O:25])[C:22]4[C:17](=[CH:18][CH:19]=[C:20](/[CH:26]=[CH:27]/[C:28]([NH:31][O:32][CH:33]5[CH2:38][CH2:37][CH2:36][CH2:35][O:34]5)=[O:29])[CH:21]=4)[O:16]3)[CH2:14][CH2:15]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 66932290HCID 66932290, compound

Product 1

HCID 87208915HCID 87208915, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(E)-3-{1′-[2-(4-Fluoro-phenyl)-ethyl]-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (300 mg, 0.673 mmol) was suspended in DCM (10 ml). TEA (0.14 ml, 1 mmol) was added and the clear solution was treated with NH2OTHP following the procedure described in Example 1, Step B, giving (E)-3-{1′-[2-(4-fluoro-phenyl)-ethyl]-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide (230 mg) as a yellow solid. The protected hydroxamic acid derivative was dissolved in DCM (10 ml) and treated with 4 M HCl in dioxane (1 ml, 4 mmol). After 1 h the solvents were evaporated, the residue was worked up with 1 M NaHCO3, extracted with DCM, which was dried and evaporated. The crude residue was purified by column chromatography (eluent: DCM/MeOH 99:1 to 90:10) to give an orange solid (95 mg) as free base.

Sources & evidence

ORD record
ord-e121be9e1bf447b48674fbc734cc0a4c
Source dataset
uspto-grants-2013_11
Patent number
US08592444B2

Reaction notes

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