Benzene, 1-bromo-4-(trifluoromethyl)- → HCID 68291725, compound

HRID 73055Notes

Reaction equation

HRID 73055 reaction equation
[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([N:13]2[CH2:18][CH2:17][C:16]3([O:23][CH:22]([CH2:24][O:25][CH3:26])[CH2:21][NH:20][CH2:19]3)[CH2:15][CH2:14]2)=[O:12])=[CH:7][C:6]=1[CH3:27])([CH3:3])[CH3:2].Br[C:29]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=1.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.CC(C)([O-])C.[Na+]>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=CC=CC=1.CN1CCCC1=O>[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([N:13]2[CH2:14][CH2:15][C:16]3([O:23][CH:22]([CH2:24][O:25][CH3:26])[CH2:21][N:20]([C:29]4[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=4)[CH2:19]3)[CH2:17][CH2:18]2)=[O:12])=[CH:7][C:6]=1[CH3:27])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 68291762HCID 68291762, compound

Product 1

HCID 68291725HCID 68291725, compoundYield 10%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

To a vial charged with (4-isopropoxy-3-methyl-phenyl)-[10-(methoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone (30.0 mg, 0.08 mmol), 1-bromo-4-(trifluoromethyl)benzene (19.7 mg, 0.088 mmol), Pd2(dba)3 (23 mg, 0.04 mmol), rac-BINAP (24.8 mg, 0.04 mmol) and sodium tert-butoxide (9.8 mg, 0.088 mmol) were added N-methyl-2-pyrrolidone (0.2 mL) and toluene (1.0 mL). The reaction mixture was heated at 100° C. under nitrogen 18 h. The reaction mixture was cooled to room temperature, filtered and purified via HPLC (1-90% CH3CN/5 mM HCl) to provide (4-isopropoxy-3-methylphenyl)(2-(methoxymethyl)-4-(4-(trifluoromethyl)phenyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methanone (5.0 mg, 0.0077 mmol, 10%). ESI-MS m/z calc. 520.2549. Found 521.3 (M+1)+; Retention time: 2.21 minutes (3 min run).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. custompurified via HPLC (1-90% CH3CN/5 mM HCl)

Sources & evidence

ORD record
ord-9d61072103d64b35a051320c3182cd28
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

Loading…