Morpholine → 4-[5-Morpholin-4-yl-2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine-1-carboxylic acid t-butyl ester

HRID 2218849Notes

Reaction equation

HRID 2218849 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18](OS(C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)(=O)=O)[CH:17]=[CH:16][C:15]=2[CH:37]2[CH2:42][C:41]([CH3:44])([CH3:43])[CH2:40][C:39]([CH3:46])([CH3:45])[CH2:38]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C(C)=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([N:47]3[CH2:52][CH2:51][O:50][CH2:49][CH2:48]3)[CH:17]=[CH:16][C:15]=2[CH:37]2[CH2:38][C:39]([CH3:46])([CH3:45])[CH2:40][C:41]([CH3:44])([CH3:43])[CH2:42]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 597694204-[5-(Nonafluorobutane-1-sulfonyloxy)-2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine-1-carboxylic acid t-butyl ester

Product 1

HCID 597693874-[5-Morpholin-4-yl-2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine-1-carboxylic acid t-butyl esterYield 74.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 7237O-XyleneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-[5-(nonafluorobutane-1-sulfonyloxy)-2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine-1-carboxylic acid t-butyl ester (200 mg, 0.286 mmol) produced in Example (81c), morpholine (37.8 mg, 0.429 mmol), sodium t-butoxide (56.7 mg, 0.572 mmol), tris(dibenzylideneacetone)dipalladium(0) (13.1 mg, 0.0143 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (11.5 mg, 0.0286 mmol) and xylene (3 mL) was stirred for 13 hours and 30 minutes at an external temperature of 100° C. under a nitrogen atmosphere. The reaction mixture was filtered through Celite to remove insoluble materials, and the filtrate was concentrated under reduced pressure. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 103 mg of the title compound as a light yellow oil.

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. customto remove insoluble materials
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-63076f28cfe141b6969d24a81bc62a90
Source dataset
uspto-grants-2008_08
Patent number
US07410971B2

Reaction notes

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