1,2-Dichloroethane → HCID 86671981, compound

HRID 874276Notes

Reaction equation

HRID 874276 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]2([CH2:20][C:19](=[O:21])[C:18]3[C:13](=[CH:14][CH:15]=[C:16](/[CH:22]=[CH:23]/[C:24](O)=[O:25])[CH:17]=3)[O:12]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:41][O:42][CH:43]1[CH2:48][CH2:47][CH2:46][CH2:45][O:44]1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][C:10]2([CH2:20][C:19](=[O:21])[C:18]3[C:13](=[CH:14][CH:15]=[C:16](/[CH:22]=[CH:23]/[C:24]([NH:41][O:42][CH:43]4[CH2:48][CH2:47][CH2:46][CH2:45][O:44]4)=[O:25])[CH:17]=3)[O:12]2)[CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67071684HCID 67071684, compound

Product 1

HCID 86671981HCID 86671981, compoundYield 72.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TEA (0.25 ml, 1.8 mmol) was added to a suspension of (E)-3-[1′-tert-butoxycarbonyl-4-oxo-spiro(chromane-2,3′-azetidine)-6-yl]-acrylic acid (430 mg, 1.20 mmol) in DCM (13 ml) and the reaction mixture was stirred at RT for 5 min. The resulting clear solution was cooled down to 0° C., EDC (344 mg, 1.80 mmol) and HOBt (243 mg, 1.80 mmol) were added and the mixture was stirred at 0° C. for 2 h. NH2OTHP (168 mg, 1.43 mmol) was added and the mixture was stirred at RT overnight. The reaction mixture was washed with 5% aqueous NaHCO3 solution and brine, the organic layer was dried over Na2SO4, filtered and evaporated. The crude residue was purified by column chromatography on silica gel (eluent: DCM/MeOH 98:2) to give (E)-3-[1′-tert-butoxycarbonyl-4-oxo-spiro(chromane-2,3′-azetidine)-6-yl]-N-(tetrahydro-pyran-2-yloxy)-acrylamide (0.40 g) as a pale yellow solid.

Workup

  1. temperatureThe resulting clear solution was cooled down to 0° C.
  2. stirringthe mixture was stirred at 0° C. for 2 h
  3. stirringthe mixture was stirred at RT overnight
  4. washThe reaction mixture was washed with 5% aqueous NaHCO3 solution and brine
  5. dry with materialthe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude residue was purified by column chromatography on silica gel (eluent: DCM/MeOH 98:2)

Sources & evidence

ORD record
ord-9273203709af4fe1b3ae4aa19f4819b4
Source dataset
uspto-grants-2015_03
Patent number
US08980877B2

Reaction notes

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