Sodium Cyanide → HCID 22270690, compound

HRID 1987307Notes

Reaction equation

HRID 1987307 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=2)[CH:10]([NH:12][C:13](=[O:28])[C:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][N:19]=2)([CH3:16])[CH3:15])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[C-:37]#[N:38].[Na+].C1OCCOCCOCCOCCOCCOC1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:36][C:33]1[CH:32]=[CH:31][C:30]([CH2:29][CH:9]([C:4]2[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([C:37]#[N:38])[CH:3]=2)[CH:10]([NH:12][C:13](=[O:28])[C:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:26])([F:27])[F:25])=[CH:20][N:19]=2)([CH3:16])[CH3:15])[CH3:11])=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 8929Sodium CyanideHCID 2855718-Crown-6HCID 22270356HCID 22270356, compound

Product 1

HCID 22270690HCID 22270690, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-[2-(3-bromo-5-fluorophenyl)-3-(4-chlorophenyl)-1-methylpropyl]-2-(5-trifluoromethyl-2-pyridyloxy)-2-methylpropanamide (Example 330, 92 mg, 0.16 mmol), sodium cyanide (12 mg, 0.24 mmol), 18-crown-6 (63 mg, 0.24 mmol) and tetrakis(triphenylphosphine)palladium (92 mg, 0.08 mmol) in 2 mL dioxane was heated under nitrogen at 100° C. for 14 h. After cooling to room temperature, the resulting mixture was partitioned between water (50 mL) and EtOAc (50 mL). The organic layer was separated, washed with water, dried over anhydrous sodium sulfate, filtered and concentrated, and the residue was purified by flash column chromatography on silica gel eluting with 30% EtOAc in hexane to afford the title compound as a racemic mixture. 1H NMR (500 MHz, CD3OD): δ 8.26 (br s, 1H), 7.96 (d, 1H), 7.93 (dd, 1H), 7.30 (br d, 1H), 7.22 (s, 1H), 7.15 (br d, 1H), 7.06 (d, 2H), 7.05 (m, 1H), 6.74 (d, 2H), 4.24 (m, 1H), 3.05 (dd, 1H), 2.91 (m, 1H), 2.63 (dd, 1H), 1.74 (s, 3H), 1.72 (s, 3H), 0.83 (d, 3H). LC-MS: m/e 534 (M+H)+ (4.2 min).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe resulting mixture was partitioned between water (50 mL) and EtOAc (50 mL)
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified by flash column chromatography on silica gel eluting with 30% EtOAc in hexane

Sources & evidence

ORD record
ord-b7a62792c92a475999bbdaff56ffd632
Source dataset
uspto-grants-2009_06
Patent number
US07550489B2

Reaction notes

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