Morpholine → 3-[4-(1-t-Butyloxycarbonyl piperidin-4-yloxy)phenyl]-1-(morpholin-4-yl)prop-2-ene-1-one

HRID 520813Notes

Reaction equation

HRID 520813 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH:21]=[CH:22][C:23]([OH:25])=O)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C(OC(Cl)=O)C.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[CH:17][C:18]([CH:21]=[CH:22][C:23]([N:39]3[CH2:44][CH2:43][O:42][CH2:41][CH2:40]3)=[O:25])=[CH:19][CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 900421133-[4-(1-t-Butyloxycarbonyl piperidin-4-yloxy)phenyl]prop-2-ene-1-oic acid

Product 1

HCID 900429883-[4-(1-t-Butyloxycarbonyl piperidin-4-yloxy)phenyl]-1-(morpholin-4-yl)prop-2-ene-1-oneYield 74.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

To a stirred solution of 3-[4-(1-t-butyloxycarbonyl piperidin-4-yloxy)phenyl]prop-2-ene-1-oic acid (38 grams, 0.109 moles, obtained in above step) and triethylamine (38.4 mL, 0.273 moles) in dichloromethane (500 mL) was added ethylchloroformate (13.6 mL, 0.142 moles) at 0° C. The reaction mass was further stirred for 2 hours at 0-5° C. Morpholine (19.2 mL, 0.219 moles) was added to above mass at 0-5° C. and the resulting mixture were stirred for 2 hours. The progress of the reaction was monitored by thin layer chromatography. After completion of reaction, the mass was quenched by adding water (100 mL). Layers were separated and the organic layer was washed with brine solution (100 mL) and dried over sodium sulphate. The organic phase was concentrated under vacuum to obtain the crude residue, which was further purified by flash chromatography using methanol:triethylamine:chloroform in the ratio of 1:1:98 to afford the title compound (34 grams).

Workup

  1. stirringthe resulting mixture were stirred for 2 hours
  2. customAfter completion of reaction
  3. customthe mass was quenched
  4. additionby adding water (100 mL)
  5. customLayers were separated
  6. washthe organic layer was washed with brine solution (100 mL)
  7. dry with materialdried over sodium sulphate
  8. concentrationThe organic phase was concentrated under vacuum
  9. customto obtain the crude residue, which
  10. customwas further purified by flash chromatography

Sources & evidence

ORD record
ord-f2a8016aa5bd47fc8ae2da33a407c692
Source dataset
uspto-grants-2016_05
Patent number
US09328092B2

Reaction notes

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