Propargyl alcohol → HCID 69099881, compound

HRID 2251530Notes

Reaction equation

HRID 2251530 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=2)[CH2:9][CH2:10][C:11]2[CH:25]=[CH:24][C:14]([O:15][C:16]([CH3:23])([CH3:22])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][CH:12]=2)=[N:6][CH:7]=1.[CH2:38]([OH:41])[C:39]#[CH:40]>CCN(CC)CC.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.[Cu]I>[OH:41][CH2:38][C:39]#[C:40][C:2]1[CH:3]=[CH:4][C:5]([N:8]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:35])[F:36])=[CH:29][CH:28]=2)[CH2:9][CH2:10][C:11]2[CH:12]=[CH:13][C:14]([O:15][C:16]([CH3:23])([CH3:22])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:24][CH:25]=2)=[N:6][CH:7]=1

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 59643326HCID 59643326, compound

Product 1

HCID 69099881HCID 69099881, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

A solution of ethyl 2-[4-(2-{(5-bromopyridin-2-yl)[4-(trifluoromethoxy)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate (500 mg; 0.86 mmol) in 3 ml of Et3N was treated under nitrogen with tetrakis(triphenylphosphine)palladium (0) (99 mg; 0.086 mmol) and copper (I) iodide (16 mg; 0.086 mmol). After stirring at rt for 5 minutes, propargyl alcohol (72 mg; 1.29 mmol) was added and the mixture heated at 65C for 7 hr. Upon cooling the reaction mixture was concentrated and the residue was partitioned between ethyl acetate and 0.1N HCl. The organic phase was washed with 0.1N HCl and brine, dried over sodium sulfate and concentrated. Purification by radial chromatography using ethyl acetate-hexane mixtures (5–50% gradient) afforded ethyl 2-[4-(2-{[5-(3-hydroxyprop-1-ynyl)pyridin-2-yl][4-(trifluoromethoxy)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate.

Workup

  1. temperatureUpon cooling the reaction mixture
  2. concentrationwas concentrated
  3. customthe residue was partitioned between ethyl acetate and 0.1N HCl
  4. washThe organic phase was washed with 0.1N HCl and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customPurification by radial chromatography

Sources & evidence

ORD record
ord-53abb0d1cda648f6a7c080adcd44e6c5
Source dataset
uspto-grants-2008_01
Patent number
US07319104B2

Reaction notes

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