4-Fluoropiperidine hydrochloride → HCID 58117377, compound

HRID 1406412Notes

Reaction equation

HRID 1406412 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]=O)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:19]1[C:20](=[O:49])[N:21]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[CH:22]=[C:23]([NH:25][C:26]([C:28]2[CH:29]=[N:30][N:31]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=3)[CH:32]=2)=[O:27])[CH:24]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[F:51][CH:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][N:55]3[CH2:56][CH2:57][CH:52]([F:51])[CH2:53][CH2:54]3)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:19]1[C:20](=[O:49])[N:21]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[CH:22]=[C:23]([NH:25][C:26]([C:28]2[CH:29]=[N:30][N:31]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=3)[CH:32]=2)=[O:27])[CH:24]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 3

HCID 27591584-Fluoropiperidine hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 86650203HCID 86650203, compound2×

Product 1

HCID 58117377HCID 58117377, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of intermediate (8f), 5-Formyl-2-[5-{[1-(4-methyl-benzyl)-1H-pyrazole-4-carbonyl]-amino}-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester, (150 mg, 0.22 mmol) in dichloromethane (10 mL) was added 4-fluoropiperidine hydrochloride (61 mg, 0.44 mmol), sodium triacetoxyborohydride (140 mg, 0.66 mmol) and acetic acid (1 drop). The reaction mixture was stirred at ambient temperature for 3 hours and then diluted with ethyl acetate. The mixture was washed with saturated aqueous sodium bicarbonate solution, brine, dried (Na2SO4) and concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 with hexane—ethyl acetate (gradient) and then ion exchange using an SCX-2 column to afford the title compound as a yellow solid, 96 mg, 57%.

Workup

  1. washThe mixture was washed with saturated aqueous sodium bicarbonate solution, brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resultant crude product was purified by flash chromatography on SiO2 with hexane—ethyl acetate (gradient)

Sources & evidence

ORD record
ord-b8b8bdb9c5914d60ae59b2da8ec93b47
Source dataset
uspto-grants-2014_12
Patent number
US08916591B2

Reaction notes

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