Nitrogen → Tert-butyl (2-chloro-5-cyano-3-(3-oxocyclohexyl)phenyl)carbamate

HRID 921927Notes

Reaction equation

HRID 921927 reaction equation
[Cl:1][C:2]1[C:7](B2OC(C)(C)C(C)(C)O2)=[CH:6][C:5]([C:17]#[N:18])=[CH:4][C:3]=1[NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].[OH-].[K+].N#N.[C:31]1(=[O:37])[CH2:36][CH2:35][CH2:34][CH:33]=[CH:32]1>CCOC(C)=O.C1CC=CCCC=C1.C1CC=CCCC=C1.[Cl-].[Cl-].[Rh].[Rh].O1CCOCC1>[Cl:1][C:2]1[C:7]([CH:33]2[CH2:34][CH2:35][CH2:36][C:31](=[O:37])[CH2:32]2)=[CH:6][C:5]([C:17]#[N:18])=[CH:4][C:3]=1[NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25]

Participants

8

Reactant 4

HCID 947NitrogenHCID 135942-Cyclohexen-1-oneHCID 14797Potassium HydroxideHCID 131734937HCID 131734937, compound

Product 1

HCID 131734953Tert-butyl (2-chloro-5-cyano-3-(3-oxocyclohexyl)phenyl)carbamateYield 41.6%

Reagents, catalysts & solvents 3

HCID 6436379Rhodium, di-mu-chlorobis((1,2,5,6-eta)-1,5-cyclooctadiene)di-CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a 20 gram dram vial was charged with tert-butyl (2-chloro-5-cyano-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (Example 573A)(379 mg, 1 mmol) and chloro(1,5-cyclooctadiene)rhodium(I) dimer (9.86 mg, 0.020 mmol). Dioxane (10 mL) was then added, followed by aq. KOH (2 M, 1 mL). The resulting solution was then evacuated and refilled with N2 before cyclohex-2-enone (144 mg, 1.500 mmol) was added via a syringe. The resulting reaction was heated at 80° C. for 1 h before it was cooled to room temperature. The reaction was diluted with EtOAc, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by flash column chromatography (0-60% EtOAc/Hexane) to give tert-butyl (2-chloro-5-cyano-3-(3-oxocyclohexyl) phenyl)carbamate (145 mg) as white foam.

Workup

  1. customThe resulting solution was then evacuated
  2. additionwas added via a syringe
  3. customThe resulting reaction
  4. temperaturewas cooled to room temperature
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by flash column chromatography (0-60% EtOAc/Hexane)

Sources & evidence

ORD record
ord-cba1ad6c20d44cf599a44491032ba8fa
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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