tert-Butyl 4-ethynylpiperidine-1-carboxylate → HCID 89558611, compound

HRID 929166Notes

Reaction equation

HRID 929166 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]=[C:15]([O:25][C@@H:26]4[CH2:30][O:29][C@@H:28]5[C@H:31]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH2:32][O:33][C@H:27]45)[N:16]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:11]3=[CH:10][C:9]=2[Cl:42])=[CH:4][CH:3]=1.[C:43]([CH:45]1[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][CH2:46]1)#[CH:44]>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C>[Si:35]([O:34][C@H:31]1[C@H:28]2[O:29][CH2:30][C@@H:26]([O:25][C:15]3[N:16]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:11]4[C:12]([N:14]=3)=[N:13][C:8]([C:5]3[CH:4]=[CH:3][C:2]([C:44]#[C:43][CH:45]5[CH2:46][CH2:47][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:49][CH2:50]5)=[CH:7][CH:6]=3)=[C:9]([Cl:42])[CH:10]=4)[C@H:27]2[O:33][CH2:32]1)([C:38]([CH3:40])([CH3:41])[CH3:39])([CH3:37])[CH3:36]

Participants

6

Reactant 2

HCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylateHCID 89558206HCID 89558206, compound

Product 1

HCID 89558611HCID 89558611, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

To a round bottom flask fitted with a reflux condenser under a nitrogen atmosphere was added 5-(4-bromophenyl)-2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine (436 mg, 0.625 mmol), tert-butyl 4-ethynylpiperidine-1-carboxylate (157 mg, 0.750 mmol), CuI (9.5 mg, 0.049 mmol), and Pd(PPh3)2Cl2 (70 mg, 0.100 mmol). Then triethylamine (4.0 mL) was added. The reaction mixture was cooled to −78°, evacuated and placed under an inert nitrogen atmosphere. Then the mixture was warmed to room temperature, and heated to 50° C. for 17 h. The mixture was allowed to cool to room temperature, and then filtered through Celite™ and rinsed with ethyl acetate until the filtrate was colorless. The filtrate was concentrated under reduced pressure. Flash silica gel chromatography of the resulting residue utilizing a Biotage™ 50 G SNAP cartridge and employing a linear gradient: 0-30% EtOAc in 1:1 Hexane/DCM over 20 column volumes afforded the desired product as a clear, colorless oil following concentration under reduced pressure. LC-MS: calculated for C42H61ClN4O7Si2 824.38, observed m/e: 825.60 (M+H)+ (Rt 3.32/4 min)

Workup

  1. customTo a round bottom flask fitted with a reflux condenser under a nitrogen atmosphere
  2. temperatureThe reaction mixture was cooled to −78°
  3. customevacuated
  4. temperatureheated to 50° C. for 17 h
  5. temperatureto cool to room temperature
  6. filtrationfiltered through Celite™
  7. washrinsed with ethyl acetate until the filtrate
  8. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-4fc3cde3f9fc4350b95d88c17424daf1
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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