3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine → HCID 59371289, compound

HRID 2095451Notes

Reaction equation

HRID 2095451 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.[F:22][C:23]([F:41])([F:40])[C:24]1[CH:39]=[CH:38][C:27]([CH2:28][O:29][CH2:30][CH2:31][CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)=[CH:26][CH:25]=1.CC(C)([O-])C.[Na+]>C1(C)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].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[CH2:34][CH2:33][CH:32]([CH2:31][CH2:30][O:29][CH2:28][C:27]3[CH:26]=[CH:25][C:24]([C:23]([F:22])([F:40])[F:41])=[CH:39][CH:38]=3)[CH2:37][CH2:36]2)[CH:7]=1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 3

HCID 154802363-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridineHCID 23676156Sodium t-butoxideHCID 593715824-[2-[4-(Trifluoromethyl)benzyloxy]ethyl]piperidine

Product 1

HCID 59371289HCID 59371289, compoundYield 111.6%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
99 °C

Procedure

To a solution of 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine (210 mg, 0.59 mmol) and 4-[2-[4-(trifluoromethyl)benzyloxy]ethyl]piperidine (186 mg, 0.65 mmol, 1.1 equiv.) in anhydrous toluene (2 mL) were added successively sodium tert-butoxide (93 mg, 0.97 mmol, 1.5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (11.8 mg, 13 μmol, 0.02 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 22.4 mg, 39 μmol, 0.06 equiv.). The mixture was degassed and purged with Ar (3 cycles), then warmed to 98-100° C. for 4 h. After cooling to room temperature, the mixture was diluted with EtOAc, and the solution was washed with brine, dried over Na2SO4, and evaporated. The residue was purified by CC on SiO2 with CH2Cl2/EtOAc 4:1, then 1:1. The product (371 mg, 100%) was obtained as a dark yellow oil.

Workup

  1. customThe mixture was degassed
  2. custompurged with Ar (3 cycles)
  3. temperatureAfter cooling to room temperature
  4. additionthe mixture was diluted with EtOAc
  5. washthe solution was washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe residue was purified by CC on SiO2 with CH2Cl2/EtOAc 4:1

Sources & evidence

ORD record
ord-91f7356bde664633b25a0417e508ff4d
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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