Cesium carbonate → HCID 71629158, compound

HRID 252128Notes

Reaction equation

HRID 252128 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.[C:9]([O:13][C:14](=[O:21])[NH:15][CH:16]1[CH2:20][CH2:19][NH:18][CH2:17]1)([CH3:12])([CH3:11])[CH3:10].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[C:9]([O:13][C:14](=[O:21])[NH:15][C@H:16]1[CH2:20][CH2:19][N:18]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=2)[CH2:17]1)([CH3:12])([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 122742,6-DibromopyridineHCID 634876Binap, (A+-)-HCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamate

Product 1

HCID 71629158HCID 71629158, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Add 2,6-dibromopyridine (500 mg, 2.11 mmol), pyrrolidin-3-ylcarbamic acid tert-butyl ester (372 mg, 2.00 mmol), tris(dibenzylideneacetone)dipalladium (0) (193 mg, 0.21 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (526 mg, 0.84 mmol), and cesium carbonate (1.37 g, 4.21 mmol) to a dry flask under nitrogen. Add degassed anhydrous toluene (10 mL) to the flask. Heat at 100° C. for one hour. Cool to room temperature and dilute with dichloromethane, filter through a pad of Celite®, concentrate to give a residue. Chromatograph the residue on silica gel eluting with 10:90 to 20:80 ethyl acetate:hexanes to give (3S)-[1-(6-bromopyridin-2-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (260 mg, 38%). 1H NMR (400 MHz, MeOH-d4) δ 7.31 (t, 1H, J=8.0 Hz), 6.66 (d, 1H, J=8.0 Hz), 6.36 (d, 1H, J=8.0 Hz), 4.22-4.16 (m, 1H), 3.68-3.64 (m, 1H), 3.56-3.49 (m, 1H), 3.47-3.41 (m, 1H), 3.26-3.22 (m, 1H), 2.26-2.18 (m, 1H), 1.98-1.90 (m, 1H), 1.44 (s, 9H).

Workup

  1. additionAdd
  2. customdegassed anhydrous toluene (10 mL) to the flask
  3. temperatureCool to room temperature
  4. additiondilute with dichloromethane
  5. filtrationfilter through a pad of Celite®
  6. concentrationconcentrate
  7. customto give a residue

Sources & evidence

ORD record
ord-6e9bdb31defb4688916dd23505269930
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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