Cesium carbonate → HCID 86708487, compound

HRID 921632Notes

Reaction equation

HRID 921632 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Br:11])[C:9]=1[F:10])[C:5]#[N:6].[C:12](=[O:19])([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[NH2:13].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>>[Br:11][C:8]1[C:9]([F:10])=[C:2]([NH:13][C:12](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH:3]=[C:4]([C:5]#[N:6])[CH:7]=1

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 83410607HCID 83410607, compound

Product 1

HCID 86708487HCID 86708487, compoundYield 59.9%

Conditions

Temperature
90 °C

Procedure

A 500 ml round bottom flask vial was loaded with 3,5-dibromo-4-fluorobenzonitrile (5.7 g, 15.53 mmol) (76% pure, rest di-bromo-regioisomer and tribromo-analog), tert-butyl carbamate (2.63 g, 22.45 mmol) palladium(ii) acetate (177 mg, 0.788 mmol), XANTPHOS (1.14 g, 1.970 mmol) and cesium carbonate (19.3 g, 59.2 mmol). The flask was evacuated and back-filled with nitrogen 2 times. 1,4-Dioxane (200 ml) was added and the flask evacuated and back-filled with nitrogen 2 times. The reaction mixture was heated (with vigorous stirring) to 90° C. for 15 hours in an oil bath. The reaction mixture was cooled to room temperature, filtered through a layer of Celite, evaporated and purified by column chromatography on silica. (750 g cartridge, gradient from 100% hexanes to 20% EtOAc in hexanes, product elutes at −17 to 21 column volumes). tert-butyl (3-bromo-5-cyano-2-fluorophenyl)carbamate (2.93 g) was isolated.

Workup

  1. customThe flask was evacuated
  2. additionback-filled with nitrogen 2 times
  3. addition1,4-Dioxane (200 ml) was added
  4. customthe flask evacuated
  5. additionback-filled with nitrogen 2 times
  6. temperatureThe reaction mixture was heated
  7. temperatureThe reaction mixture was cooled to room temperature
  8. filtrationfiltered through a layer of Celite
  9. customevaporated
  10. custompurified by column chromatography on silica

Sources & evidence

ORD record
ord-3f126c3e14374eef88381b64e5d61a56
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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