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3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine → HCID 59371473, compound

HRID 2095388
Notes
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Reaction equation

HRID 2095388 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.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][O:29][CH2:30][CH2:31][CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[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[CH2:34][CH2:33][CH:32]([CH2:31][CH2:30][O:29][CH2:28][C:24]3[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=3)[CH2:37][CH2:36]2)[CH:7]=1)=[O:16])([CH3:21])([CH3:20])[CH3:19]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 3

HCID 154802363-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridineHCID 23665647Potassium tert-butoxideHCID 593713854-[2-(3-Pyridylmethoxy)ethyl]piperidine

Product 1

HCID 59371473HCID 59371473, compoundYield 89.4%

Reagents, catalysts & solvents 4

HCID 636044
1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)
Catalyst
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst
HCID 1140TolueneSolvent
HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine (147 mg, 0.41 mmol) and 4-[2-(3-pyridylmethoxy)ethyl]piperidine (99.8 mg, 0.45 mmol, 1.1 equiv.) in anhydrous toluene (2 mL) were added successively potassium tert-butoxide (75 mg, 0.61 mmol, 1.5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (7.5 mg, 8.0 μmol, 0.02 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 14.3 mg, 24 μmol, 0.06 equiv.). 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 (SiO2, CH2Cl2/EtOAc 4:1 followed by CH2Cl2/MeOH 10:1). The product (182 mg, 89%) was obtained as a pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ 8.56 (br, 2H), 7.80 (m, 3H), 7.46 (m, 1H), 6.94 (m, 1H), 4.51 (s, 2H), 4.12 (m, 2H), 3.83 (m, 1H), 3.66 (m, 2H), 3.54 (m, 2H), 3.39 (m, 2H), 2.76 (t, 2H, J=11.2 Hz), 2.01-1.80 (m, 5H), 1.63 (m, 4H), 1.46 (s, 9H), 1.33 (m, 2H).

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 (SiO2, CH2Cl2/EtOAc 4:1 followed by CH2Cl2/MeOH 10:1)

Sources & evidence

ORD record
ord-9d94b420c43f45bd9b201bd49d954072
Source dataset
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08445684B2

Reaction notes

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