Sodium Bicarbonate → tert-butyl 4-(4-(5-fluoro-2-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)piperidine-1-carboxylate

HRID 527989

Reaction equation

HRID 527989 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[C:9]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C(=O)(O)[O-].[Na+].[F:29][C:30]1[CH:31]=[CH:32][C:33]([O:39][CH3:40])=[C:34](B(O)O)[CH:35]=1>CN(C)C=O.O.C(OCC)(=O)C.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.[Cl-].[Cl-].[Fe+2].[Pd+2]>[F:29][C:30]1[CH:35]=[CH:34][C:33]([O:39][CH3:40])=[C:32]([C:2]2[C:3]3[CH:10]=[C:9]([CH:11]4[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]4)[NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:31]=1

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 90418107tert-butyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)piperidine-1-carboxylate

Product 1

HCID 90418838tert-butyl 4-(4-(5-fluoro-2-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 53384307Dichloro[1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of Example 1C (200 mg, 0.6 mmol) in N,N-dimethylformamide (8 mL), was added a solution of sodium bicarbonate (0.118 g, 1.404 mmol) in 0.5 mL water followed by 5-fluoro-2-methoxyphenylboronic acid (204 mg, 1.2 mmol). The mixture was degassed with nitrogen and [1,1′-bis(di tert butyl phosphino)ferrocene]palladium(II) dichloride (21 mg, 0.033 mmol) was added. The mixture was heated under microwave conditions (Biotage Initiator) at 100° C. for 1 hour. The mixture was diluted with ethyl acetate and filtered through diatomaceous earth. The organic layer was washed with water and brine, dried over sodium sulfate, filtered, concentrated and purified by column chromatography (silica gel, 40% ethyl acetate-hexane) to afford the title compound. LCMS: 427.21 (M+1)+.

Workup

  1. additionwas added
  2. filtrationfiltered through diatomaceous earth
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography (silica gel, 40% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-8b01117117ae4def8e3a9bfba393835a
Source dataset
uspto-grants-2016_05
Patent number
US09346813B2

Linked notes

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