1,2-Dichloroethane → HCID 87258296, compound

HRID 874257Notes

Reaction equation

HRID 874257 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH2:7][C:6]2([CH2:18][C:17](=[O:19])[C:16]3[C:11](=[CH:12][CH:13]=[C:14](/[CH:20]=[CH:21]/[C:22](O)=[O:23])[CH:15]=3)[O:10]2)[CH2:5]1)(=[O:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:39][O:40][CH:41]1[CH2:46][CH2:45][CH2:44][CH2:43][O:42]1>C(Cl)Cl>[C:1]([N:4]1[CH2:9][CH2:8][CH2:7][C:6]2([CH2:18][C:17](=[O:19])[C:16]3[C:11](=[CH:12][CH:13]=[C:14](/[CH:20]=[CH:21]/[C:22]([NH:39][O:40][CH:41]4[CH2:46][CH2:45][CH2:44][CH2:43][O:42]4)=[O:23])[CH:15]=3)[O:10]2)[CH2:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67071460HCID 67071460, compound

Product 1

HCID 87258296HCID 87258296, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(±)-(E)-3-[1′-Acetyl-4-oxo-spiro(chromane-2,3′-piperidine)-6-yl]-acrylic acid (crude compound from STEP B, 590 mg) was dissolved in DCM (30 ml) and TEA (0.498 ml, 3.59 mmol). EDC (513 mg, 2.68 mmol) and HOBt (362 mg, 2.68 mmol) were added and the mixture was stirred for 10 min at RT. NH2OTHP (251 mg, 2.15 mmol) was added and the solution was stirred overnight at RT and was then partitioned between 5% NaHCO3 and DCM. The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness. The crude mixture was purified by column chromatography (eluent: DCM/MeOH 99:1 to 97:3) to give (±)-(E)-3-[1′-acetyl-4-oxo-spiro(chromane-2,3′-piperidine)-6-yl]-N-(tetrahydro-pyran-2-yloxy)-acrylamide that was dissolved in DCM and treated with 4 M HCl in dioxane for 3 h. The precipitate was collected by filtration and washed with DCM to give (±)-(E)-3-[1′-acetyl-4-oxo-spiro(chromane-2,3′-piperidine)-6-yl]-N-hydroxy-acrylamide as pale yellow powder (404 mg).

Workup

  1. stirringthe solution was stirred overnight at RT
  2. customwas then partitioned between 5% NaHCO3 and DCM
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness
  6. customThe crude mixture was purified by column chromatography (eluent: DCM/MeOH 99:1 to 97:3)

Sources & evidence

ORD record
ord-a2afa135eabd47309270da6163df8db3
Source dataset
uspto-grants-2015_03
Patent number
US08980877B2

Reaction notes

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