Cesium fluoride → Tert-butyl 4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-carboxylate

HRID 731556Notes

Reaction equation

HRID 731556 reaction equation
Br[C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1.[Cl:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.[F-].[Cs+]>COCCOC>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:2]2[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=2[CH2:4][N:5]2[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]2)=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 742994-Chlorophenylboronic acidHCID 20754660Tert-butyl 4-(2-bromobenzyl)piperazine-1-carboxylate

Product 1

HCID 22662065Tert-butyl 4-((4'-chlorobiphenyl-2-yl)methyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of EXAMPLE 22A (5.82 g, 16.394 mmol) in DME (80 mL) was treated with 4-chlorophenylboronic acid (3.089 g, 19.673 mmol), CsF (7.476 g, 49.182 mmol) and (Ph3P)2Pd(OAc)2 (1.228 g, 1.639 mmol), heated to reflux for 4 hours, and filtered. The filtrate was partitioned between aqueous NaHCO3 and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined extracts were dried (MgSO4), filtered, and concentrated. The residue was purified by silica gel column chromatography with 15% ethyl acetate/hexane to provide the desired product. MS (ESI) m/e 386, 388 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 4 hours
  3. filtrationfiltered
  4. customThe filtrate was partitioned between aqueous NaHCO3 and ethyl acetate
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe combined extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography with 15% ethyl acetate/hexane

Sources & evidence

ORD record
ord-c073f31f8f5141d58bab2a75e8cd5627
Source dataset
uspto-grants-2009_09
Patent number
US07585858B2

Reaction notes

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