tert-Butyl bromoacetate → HCID 86623477, compound

HRID 1992658Notes

Reaction equation

HRID 1992658 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[C:13]([O:17][C:18](=[O:21])[CH2:19]Br)([CH3:16])([CH3:15])[CH3:14]>CCOC(C)=O.O.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.[Pd].C(P([C-]1C=CC=C1)C(C)(C)C)(C)(C)C.C1(C2[C-](C3C=CC=CC=3)C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C=2C2C=CC=CC=2)C=CC=CC=1.[Fe+2].[Zn]>[C:13]([O:17][C:18](=[O:21])[CH2:19][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([Cl:1])[CH:7]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

8

Reactant 2

HCID 79177tert-Butyl bromoacetateHCID 27737912-Chloro-4-iodo-5-(trifluoromethyl)pyridine

Product 1

HCID 86623477HCID 86623477, compound

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 72499888Dibenzalacetone palladiumCatalyst2×HCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Under an atmosphere of dry argon, a mixture of palladium dibenzylideneacetone (Pd2(dba)3, 22 mg, 0.02 mmol), di-tert-butylphosphino pentaphenylferrocene (17 mg, 0.02 mmol), 2-chloro-4-iodo-5-trifluoromethyl-pyridine (1.50 g, 4.88 mmol) and the Reformatzky reagent prepared from bromo-acetic acid tert-butyl ester and activated zinc metal (1.40 g, 5.37 mmol) is suspended in dry and degassed THF (20 ml). The mixture is heated to 60° C. After 45 minutes and after 90 minutes, additional batches of palladium dibenzylideneacetone (Pd2(dba)3, 22 mg, 0.02 mmol), di-tert-butylphosphino pentaphenylferrocene (17 mg, 0.02 mmol), and of the Reformatzky reagent (1.40 g, 5.37 mmol) are added. After a total of 2.5 h at 60° C., TLC analysis indicated complete conversion of starting materials. Upon cooling to RT, the reaction mixture is diluted with equal amounts of EtOAc and H2O, and filtered through a tight plug of cotton. The organic layer is separated, washed with brine twice, dried over Na2SO4, and the solvent is evaporated. The residue is purified by FCC (hexanes/EtOAc, gradient from 100:0 to 97:3) to afford the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.44 (s, 9H), 3.71 (s, 2H), 7.39 (s, 1H), 8.63 (s, 1H). ES+−MS: 294.1, 296.2 (Cl) [M+H]+.

Workup

  1. customin dry
  2. customdegassed THF (20 ml)
  3. waitafter 90 minutes
  4. customAfter a total of 2.5 h
  5. customat 60° C.
  6. temperatureUpon cooling to RT
  7. filtrationfiltered through a tight plug of cotton
  8. customThe organic layer is separated
  9. washwashed with brine twice
  10. dry with materialdried over Na2SO4
  11. customthe solvent is evaporated
  12. customThe residue is purified by FCC (hexanes/EtOAc, gradient from 100:0 to 97:3)

Sources & evidence

ORD record
ord-ce37a75229774bfa8095615a3ddb458d
Source dataset
uspto-grants-2010_01
Patent number
US07648989B2

Reaction notes

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