1-Bromo-3-chlorobenzene → tert-Butyl 1-(3-chlorophenyl)pyrrolidin-3-ylcarbamate

HRID 1048103Notes

Reaction equation

HRID 1048103 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][CH:9]1[CH2:13][NH:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])[CH3:3].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:21]1[CH:22]=[C:23]([Cl:27])[CH:24]=[CH:25][CH:26]=1.C1(P(C2C=CC=CC=2)C2(P(C3C=CC=CC=3)C3C=CC=CC=3)CC=C3C(C=CC=C3)=C2C2C3C(=CC=CC=3)C=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:27][C:23]1[CH:22]=[C:21]([N:12]2[CH2:11][CH2:10][CH:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])[CH2:13]2)[CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 79281-Bromo-3-chlorobenzeneHCID 10796Cesium carbonateHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 86595863(+/-)-2,2-Bis(diphenylphosphino)-1,1-binaphthyl

Product 1

HCID 67165871tert-Butyl 1-(3-chlorophenyl)pyrrolidin-3-ylcarbamateYield 62.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

3-N-Boc-amino pyrrolidine (120 mg, 0.644 mmol), cesium carbonate (252 mg, 0.773 mmol), and 3-bromochlorobenzene (75.7 μl, 0.644 mmol) were suspended in dry toluene. Argon was bubbled through the suspension for 2 minutes and then tris(dibenyzlideneacetone)dipalladium (35.4 mg, 0.0387 mmol) and rac-2,2-bis(diphenylphosphino)-1,1′-binaphthyl (60.4 mg, 0.0966 mmol) were added. The reaction vial was capped and heated to 110° C. with rapid stirring. After 15 hours, reaction was cooled to ambient temperature and applied directly to a silica gel column. Elution was a gradient of 5-70% ethyl acetate-hexanes provided the title compound (120 mg, 0.404 mmol, 62.8% yield) as an oil.

Workup

  1. customArgon was bubbled through the suspension for 2 minutes
  2. customThe reaction vial was capped
  3. customreaction
  4. temperaturewas cooled to ambient temperature
  5. washElution

Sources & evidence

ORD record
ord-96352dc313544f70abb2f73b99053bb9
Source dataset
uspto-grants-2013_10
Patent number
US08569522B2

Reaction notes

Loading…