1-Bromo-2,4-difluorobenzene → HCID 68416544, compound

HRID 2239798Notes

Reaction equation

HRID 2239798 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1Br.[N:10]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15][CH2:14][NH:13][CH2:12][CH2:11]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.[K+]>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>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:13]1[CH2:14][CH2:15][CH2:16][N:10]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:11][CH2:12]1

Participants

7

Reactant 4

HCID 676741-Bromo-2,4-difluorobenzeneHCID 634876Binap, (A+-)-HCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 68416544HCID 68416544, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

2,4-Difluorobromobenzene (2 mmol), t-butyl 1,4-diazepane-1-carboxylate (3 mmol), Pd2(dba)3 (0.04 mmol, 4 mol % Pd, 36 mg), BINAP (0.08 mmol, 50 mg), potassium t-butoxide (KO-t-Bu, 2.8 mmol, 314 mg), and toluene (10 mL) are added to an oven-dried Schienk flask that is purged with argon for approximately 15 min. The reaction mixture is then heated to 90° C. under argon until all of 2.4-difluorobromobenzene is consumed as determined by GC analysis. The reaction mixture is then allowed to cool to RT, diluted with EtOAc (20 mL) and filtered through a Celite pad. The filtrate is evaporated, and purified by silica gel column chromatography to afford t-butyl 4-(2,4-difluorophenyl)-1,4-diazepane-1-carboxylate which is deprotected by TFA in DCM. The reaction mixture is concentrated and the residue is extracted twice with DCM to afford 1-(2,4-difluorophenyl)-1,4-diazepane as a yellow oil: LC/MS (M+1=213.31). 1H NMR (CDCl3, 400 MHz) δ 1.82 (br s, 1H, NH), 1.91 (quintuplet, 2H, J=6.0 Hz), 2.97 (t, 2H, J=5.6 Hz), 3.05 (t, 2H, J=5.2 Hz), 3.33 (m, 4H), 6.70-6.87 (m, 3H).

Workup

  1. customis purged with argon for approximately 15 min
  2. customis consumed
  3. temperatureto cool to RT
  4. additiondiluted with EtOAc (20 mL)
  5. filtrationfiltered through a Celite pad
  6. customThe filtrate is evaporated
  7. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-b7ccf4f0e0174288a9163d6cc1552d35
Source dataset
uspto-grants-2010_05
Patent number
US07723343B2

Reaction notes

Loading…