3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine → HCID 59371275, compound

HRID 2095425Notes

Reaction equation

HRID 2095425 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([O:8][CH2:9][C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH:7]=1.[C:22]1([CH2:28][CH2:29][CH2:30][CH2:31][CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1.CCOC(C)=O.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].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[C:18]([O:17][C:15]([N:11]1[CH2:12][CH2:13][CH2:14][C@H:10]1[CH2:9][O:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([N:35]2[CH2:36][CH2:37][CH:32]([CH2:31][CH2:30][CH2:29][CH2:28][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:33][CH2:34]2)[CH:7]=1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

8

Reactant 3

HCID 154802363-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridineHCID 221110404-(4-Phenylbutyl)piperidineHCID 23665647Potassium tert-butoxide

Product 1

HCID 59371275HCID 59371275, compoundYield 74.1%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine (125 mg, 350 μmol) and 4-(4-phenylbutyl)piperidine (83.4 mg, 384 μmol, 1.1 equiv.) in anhydrous toluene (2 mL) were added successively potassium tert-butoxide (64 mg, 0.52 mmol, 1.5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (6.4 mg, 7.0 μmol, 0.02 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 12.1 mg, 21 μmol, 55 mequiv.). The mixture was degassed and purged with Ar (3 cycles), then warmed by microwave irradiation under Ar. After reaction for 30-40 minutes at 130° C., the mixture was cooled to room temperature, diluted with EtOAc, and washed with brine. The solution was dried over Na2SO4 and evaporated, and the residue was purified by CC on SiO2 with CH2Cl2/EtOAc 3:2. 3-[[1-(tert-Butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-5-[4-(4-phenylbutyl)-1-piperidinyl]pyridine (128 mg, 74%) was obtained as a pale yellow oil.

Workup

  1. customThe mixture was degassed
  2. custompurged with Ar (3 cycles)
  3. temperaturewarmed by microwave irradiation under Ar
  4. customAfter reaction for 30-40 minutes at 130° C.
  5. washwashed with brine
  6. dry with materialThe solution was dried over Na2SO4
  7. customevaporated
  8. customthe residue was purified by CC on SiO2 with CH2Cl2/EtOAc 3:2

Sources & evidence

ORD record
ord-a37605bf7f104c77b72729e088dfb151
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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