Sodium Carbonate → 7-Fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one

HRID 2223088Notes

Reaction equation

HRID 2223088 reaction equation
Cl[C:2]1[C:8]2[CH:9]=[C:10]([F:13])[CH:11]=[CH:12][C:7]=2[N:6]([CH3:14])[C:5](=[O:15])[CH2:4][N:3]=1.C([O-])([O-])=O.[Na+].[Na+].[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:13][C:10]1[CH:11]=[CH:12][C:7]2[N:6]([CH3:14])[C:5](=[O:15])[CH2:4][N:3]=[C:2]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:8]=2[CH:9]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 597138735-Chloro-7-fluoro-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

Product 1

HCID 443661797-Fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-oneYield 76%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

As illustrated in the scheme above and following General Procedure 4, 5-chloro-7-fluoro-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (0.201 g, 0.887 mmol), Na2CO3 (0.0940 g, 0.887 mmol), PdCl2(dppf) (0.0362. g, 0.0443 mmol) and phenylboronic acid (0.108 g, 0.886 mmol) were combined and heated for 13 h. After workup, purification of the crude product by silica gel column chromatography (3:1 CH2Cl2:EtOAc) provided the title compound (0.180 g, 76%). 1H-NMR (CDCl3): δ 7.64-7.60 (m, 2H), 7.51-7.45 (m, 1H), 7.44-7.39 (m, 2H), 7.34 (dd, J=4.8 Hz, J=9.2 Hz, 1H), 7.31-7.25 (m, 1H), 7.02 (dd, J=2.8 Hz, J=8.8 Hz, 1H), 4.84 (d, J=10.8 Hz, 1H), 3.78 (d, J=10.8 Hz, 1H), 3.40 (s, 3H). MS (ESI) (M+H)+=269.

Workup

  1. temperatureheated for 13 h
  2. customAfter workup, purification of the crude product by silica gel column chromatography (3:1 CH2Cl2:EtOAc)

Sources & evidence

ORD record
ord-94315c751e8b4bf9b15ab6a8f5b6c851
Source dataset
uspto-grants-2008_05
Patent number
US07375101B2

Reaction notes

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