Dimethylformamide → HCID 18628683, compound

HRID 1060749Notes

Reaction equation

HRID 1060749 reaction equation
[C:1]([CH2:3][NH:4][C:5](=[O:26])[CH:6]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[CH:12]=1)[CH2:7][CH:8]([CH3:10])[CH3:9])#[N:2].Br[C:28]1[CH:42]=[CH:41][C:31]([CH2:32][NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:30][CH:29]=1.C(=O)(O)[O-].[Na+].CN(C=O)C>O.[Pd](Cl)Cl>[C:1]([CH2:3][NH:4][C:5]([CH:6]([C:11]1[CH:12]=[C:13]([C:28]2[CH:29]=[CH:30][C:31]([CH2:32][NH:33][C:34](=[O:40])[O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[CH:41][CH:42]=2)[CH:14]=[CH:15][CH:16]=1)[CH2:7][CH:8]([CH3:9])[CH3:10])=[O:26])#[N:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 10959214HCID 10959214, compoundHCID 12453839tert-butyl N-[(4-bromophenyl)methyl]carbamate

Product 1

HCID 18628683HCID 18628683, compoundYield 82.1%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolvent

Conditions

Temperature
82.5 °C

Procedure

A mixture comprised of N-cyanomethyl-4-methyl-2-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]pentanamide (250 mg, 0.702 mmol), tert-butyl 4-bromobenzylcarbamate (303 mg, 1.053 mmol), sodium bicarbonate (1.1 mL, 2.11 mmol), palladium(II) chloride (18 mg, 0.0211 mmol) and DMF (15.8 mL) was stirred under nitrogen at between 80-85° C. until the reaction was complete. The mixture was diluted with water and the product was extracted with diethyl ether (3×). The combined extracts were washed with brine, dried (MgSO4) and then concentrated in vacuo. The product was purified from the residue by flash chromatography over silica gel (ethyl acetate/hexanes) to provide tert-butyl 3′-(1-cyanomethylcarbamoyl-3-methylbutyl)biphenyl-4-ylmethylcarbamate (252 mg, 0.576 mmol). 1H NMR (400 MHz, d6-DMSO): δ 8.79 (br s, 1H), 7.58-7.26 (m, 9H), 4.16 (d, J=5.2 Hz, 2H), 4.11 (br s, 2H), 3.67 (dd, J=7.2, 7.2 Hz, 1H), 1.95-1.91 (m, 1H), 1.57-1.53 (m, 1H), 1.40-1.33 (m, 10H), 0.88 (dd, J=6.7, 6.7 Hz, 6H); MS (−ESI) m/z 434.6 (M−H)−.

Workup

  1. extractionthe product was extracted with diethyl ether (3×)
  2. washThe combined extracts were washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe product was purified from the residue by flash chromatography over silica gel (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ebd0d30d5ffd450e9ab3e9ef5cb9f6f3
Source dataset
uspto-grants-2003_02
Patent number
US06525036B2

Reaction notes

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