1,2-Dichloroethane → HCID 87208874, compound

HRID 2046727Notes

Reaction equation

HRID 2046727 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[CH2:13][CH2:12][C:11]2([CH2:22][C:21](=[O:23])[C:20]3[C:15](=[CH:16][CH:17]=[C:18](/[CH:24]=[CH:25]/[C:26]([OH:28])=O)[CH:19]=3)[O:14]2)[CH2:10][CH2:9]1.C(Cl)CCl.[NH2:33][O:34]C1CCCCO1>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[CH2:13][CH2:12][C:11]2([CH2:22][C:21](=[O:23])[C:20]3[C:15](=[CH:16][CH:17]=[C:18](/[CH:24]=[CH:25]/[C:26]([NH:33][OH:34])=[O:28])[CH:19]=3)[O:14]2)[CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 66932444HCID 66932444, compound

Product 1

HCID 87208874HCID 87208874, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(E)-3-{1′-(pyridin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (133 mg, crude compound from STEP B) was dissolved in DCM (4 ml) and TEA (0.098 ml, 0.704 mmol). EDC (101 mg, 0.53 mmol) HOBT (71 mg, 0.53 mmol) and NH2OTHP (49 mg, 0.42 mmol) were added, the mixture was stirred at RT overnight and then partitioned between water and DCM. The organic phase was dried over Na2SO4 and evaporated. The crude residue was purified by column chromatography (eluent:DCM/MeOH/NH4OH 96:4:0.2) and the resulting (E)-3-{1′-(pyridin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide was dissolved in DCM and treated with HCl/Et2O for 4 h. The precipitate was filtered and washed with DCM to give (E)-3-{1′-(pyridin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-hydroxy-acrylamide as its di-hydrochloride (66 mg, white powder).

Workup

  1. custompartitioned between water and DCM
  2. dry with materialThe organic phase was dried over Na2SO4
  3. customevaporated
  4. customThe crude residue was purified by column chromatography (eluent:DCM/MeOH/NH4OH 96:4:0.2)
  5. dissolutionthe resulting (E)-3-{1′-(pyridin-2-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide was dissolved in DCM
  6. additiontreated with HCl/Et2O for 4 h
  7. filtrationThe precipitate was filtered
  8. washwashed with DCM

Sources & evidence

ORD record
ord-6c2a67bfe0724960a0229439b871300c
Source dataset
uspto-grants-2013_11
Patent number
US08592444B2

Reaction notes

Loading…