1,2-Dimethoxyethane → tert-butyl ((5-(cyclohex-1-en-1-yl)-1-((3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate

HRID 1051019Notes

Reaction equation

HRID 1051019 reaction equation
Br[C:2]1[N:6]([S:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[CH:11]=2)(=[O:9])=[O:8])[CH:5]=[C:4]([CH2:23][N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH:3]=1.[C:33]1(B2OC(C)(C)C(C)(C)O2)[CH2:38][CH2:37][CH2:36][CH2:35][CH:34]=1.C(=O)([O-])[O-].[K+].[K+].COCCOC>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[C:33]1([C:2]2[N:6]([S:7]([C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH:17]4[CH2:22][CH2:21][CH2:20][CH2:19][O:18]4)[CH:11]=3)(=[O:8])=[O:9])[CH:5]=[C:4]([CH2:23][N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[CH:3]=2)[CH2:38][CH2:37][CH2:36][CH2:35][CH:34]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 109326752-(Cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 118477104tert-butyl ((5-bromo-1-((3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate

Product 1

HCID 90168925tert-butyl ((5-(cyclohex-1-en-1-yl)-1-((3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

tert-Butyl ((5-bromo-1-((3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate 7b (770 mg, 1.5 mmol), 2-(cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (394 mg, 1.4 mmol, prepared by a known method disclosed in “Journal of the American Chemical Society, 2002, 124(27), 8001-8006”), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (53 mg, 0.07 mmol) and potassium carbonate (401 mg, 2.9 mmol) were successively added to 15 mL of a mixed solvent of ethylene glycol dimethyl ether and water (V/V=3:1), then the reaction solution was heated up to 100° C. and stirred for 10 h. 15 mL of water were added, and the reaction solution was extracted with ethyl acetate (50 mL×4). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography with elution system C to obtain the title product tert-butyl ((5-(cyclohex-1-en-1-yl)-1-((3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)sulfonyl)-1H-pyrrol-3-yl)methyl)(methyl)carbamate 7c (554 mg, a light yellow oil) in 72% yield.

Workup

  1. extractionthe reaction solution was extracted with ethyl acetate (50 mL×4)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography with elution system C

Sources & evidence

ORD record
ord-d3936a5aa1084dd49af11ab6e78c309a
Source dataset
uspto-grants-2016_07
Patent number
US09388133B2

Reaction notes

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