Morpholine → HCID 44247845, compound

HRID 1868154Notes

Reaction equation

HRID 1868154 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])[CH2:13][C@H:12]2[CH3:28])(=[O:10])=[O:9])=[C:4]([Cl:29])[CH:3]=1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[NH:82]1[CH2:87][CH2:86][O:85][CH2:84][CH2:83]1>CCOC(C)=O.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]>[Cl:29][C:4]1[CH:3]=[C:2]([N:82]2[CH2:87][CH2:86][O:85][CH2:84][CH2:83]2)[CH:7]=[CH:6][C:5]=1[S:8]([N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[C:24]([F:27])([F:26])[F:25])[CH2:13][C@H:12]1[CH3:28])(=[O:10])=[O:9]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 44248096HCID 44248096, compound

Product 1

HCID 44247845HCID 44247845, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A 5-mL microwave vial was charged with a stirbar, (2R)-1-[(4-bromo-2-chlorophenyl)sulfonyl]-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazine (250 mg, 0.49 mmol), Sodium tert-butoxide (77 mg, 0.74 mmol), BINAP (31 mg, 0.05 mmol), and Pd2(dba)3 (25 mg, 0.03 mmol). The vial was sealed and vacuum-purged with N2 three times. Toluene (2.0 mL) was then added under N2, followed by morpholine (0.05 mL, 0.53 mmol). The reaction mixture was heated to 75° C. under thermal conditions for 30 minutes, upon which the reaction was judged complete by LCMS. The reaction mixture was diluted with EtOAc (100 mL), and filtered through celite to remove inorganics. The filtrate was concentrated in vacuo and the crude product was directly loaded onto a SiO2 column and purified via normal phase chromatography (5%-50% EtOAc/Hexanes gradient), affording the desired compound in >95% purity. HRMS: calcd for C22H24ClF4N3O3S+H+, 522.12358. found ([M+H]+), 522.12358. HPLC Method 1: room temperature, 7.125 min, 100%. HPLC Method 2: room temperature, 7.664 min, 100%.

Workup

  1. customThe vial was sealed
  2. customvacuum-purged with N2 three times
  3. additionToluene (2.0 mL) was then added under N2
  4. filtrationfiltered through celite
  5. customto remove inorganics
  6. concentrationThe filtrate was concentrated in vacuo
  7. custompurified via normal phase chromatography (5%-50% EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-2aa0541cd220491bb88ebce307c7c38b
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

Loading…