Cyclobutanone → 3-[4-(1-Cyclobutyl piperidin-4-yloxy)phenyl]-1-(morpholin-4-yl)prop-2-ene-1-one

HRID 520817Notes

Reaction equation

HRID 520817 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH:15]1[CH2:20][CH2:19][CH:18]([O:21][C:22]2[CH:27]=[CH:26][C:25]([CH:28]=[CH:29][C:30]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[O:31])=[CH:24][CH:23]=2)[CH2:17][CH2:16]1.[C:38]1(=O)[CH2:41][CH2:40][CH2:39]1>ClC(Cl)C>[CH:38]1([N:15]2[CH2:16][CH2:17][CH:18]([O:21][C:22]3[CH:27]=[CH:26][C:25]([CH:28]=[CH:29][C:30]([N:32]4[CH2:37][CH2:36][O:35][CH2:34][CH2:33]4)=[O:31])=[CH:24][CH:23]=3)[CH2:19][CH2:20]2)[CH2:41][CH2:40][CH2:39]1

Participants

5

Reactant 3

HCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 900427143-[4-(Piperidin-4-yloxy)phenyl]-1-(morpholin-4-yl)prop-2-ene-1-one

Product 1

HCID 900417633-[4-(1-Cyclobutyl piperidin-4-yloxy)phenyl]-1-(morpholin-4-yl)prop-2-ene-1-oneYield 78.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (38.6 grams, 0.18 moles) was added in a single lot to a well stirred solution of 3-[4-(Piperidin-4-yloxy)phenyl]-1-(morpholin-4-yl)prop-2-ene-1-one (19.1 grams, 0.060 moles, obtained in preparation 1) and cyclobutanone (6.8 mL, 0.09 moles) in dichloroethane (500 mL). The mixture was further stirred at room temperature for 6 hours. The progress of the reaction was monitored by thin layer chromatography. After completion of reaction, the mass was quenched on to water (1000 mL) and basified with 40% lye solution (pH˜9). The layers were separated and the aqueous layer was extracted with dichloromethane (2×200 mL). The combined organic layer was washed with brine solution (250 mL), dried over sodium sulfate, concentrated under vacuum and the residual mass was further purified by flash chromatography using methanol:triethylamine:chloroform in the ratio of 1.5:0.25:98.25 to obtain the title compound (17.4 grams).

Workup

  1. customAfter completion of reaction
  2. customthe mass was quenched on to water (1000 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (2×200 mL)
  5. washThe combined organic layer was washed with brine solution (250 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customthe residual mass was further purified by flash chromatography

Sources & evidence

ORD record
ord-a6f2db23969d48f0b696cca26d22bb19
Source dataset
uspto-grants-2016_05
Patent number
US09328092B2

Reaction notes

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