3-Bromopyridine → 1,1-Dimethylethyl 1-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane-7-carboxylate

HRID 2076400Notes

Reaction equation

HRID 2076400 reaction equation
[CH2:1]1[C:5]2([CH2:9][CH2:8][CH2:7][NH:6]2)[CH2:4][CH2:3][N:2]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].Br[C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1.CC(C)([O-])C.[K+].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>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].O.C1(C)C=CC=CC=1>[N:20]1[CH:21]=[CH:22][CH:23]=[C:18]([N:6]2[CH2:7][CH2:8][CH2:9][C:5]32[CH2:1][N:2]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:3][CH2:4]3)[CH:19]=1

Participants

8

Reactant 4

HCID 122863-BromopyridineHCID 634876Binap, (A+-)-HCID 22291199tert-Butyl 1,7-diazaspiro[4.4]nonane-7-carboxylate2×HCID 23665647Potassium tert-butoxide

Product 1

HCID 222911941,1-Dimethylethyl 1-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane-7-carboxylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
180 °C

Procedure

A mixture of tert-butyl 2,6-diazaspiro[4.4]nonane-2-carboxylate (1.00 g, ˜4.4 mmol), 3-bromopyridine (0.736 g, 4.66 mmol), potassium tert-butoxide (1.22 g, 10.9 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.155 g, 0.169 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.158 g, 0.254 mmol) and dry toluene (25 mL) was placed in a pressure tube under argon. The mixture was stirred and heated at 180° C. (bath temperature) for 8 h and cooled. Thin layer analysis indicated that very little conversion had taken place. A second charge, equal in quantity to the first, of all reagents except the tert-butyl 2,6-diazaspiro[4.4]nonane-2-carboxylate was added to pressure tube and the tube was returned to the bath for another 8 h. Again relatively little reaction seemed to have occurred, so a third charge of reagents was added and heating (at 180° C.) was continued for a third 8 h period. Water (20 mL) was added and the mixture was extracted with ethyl acetate (6×25 mL). The extracts were dried (K2CO3) and concentrated. Column chromatography of the residue on Merck silica gel 60 (70-230 mesh), with 6:4 (v/v) chloroform/acetone, gave 150 mg (˜11%) of light brown oil, after concentration of selected fractions.

Workup

  1. customwas placed in a pressure tube under argon
  2. temperaturecooled
  3. customAgain relatively little reaction
  4. additionso a third charge of reagents
  5. additionwas added
  6. temperatureheating (at 180° C.)
  7. customwas continued for a third 8 h period
  8. extractionthe mixture was extracted with ethyl acetate (6×25 mL)
  9. dry with materialThe extracts were dried (K2CO3)
  10. concentrationconcentrated
  11. customColumn chromatography of the residue on Merck silica gel 60 (70-230 mesh), with 6:4 (v/v) chloroform/acetone, gave 150 mg (˜11%) of light brown oil

Sources & evidence

ORD record
ord-293d21800e8c4f078b7c1e418acb20ff
Source dataset
uspto-grants-2011_04
Patent number
US07923559B2

Reaction notes

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