Water → HCID 86583543, compound

HRID 1016770Notes

Reaction equation

HRID 1016770 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]([C:16]2[CH:21]=[C:20]([C:22]#[C:23][Si](C)(C)C)[CH:19]=[C:18]([CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)[CH:17]=2)[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:5][CH:4]=1)#[N:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][CH:10]([C:16]2[CH:17]=[C:18]([CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33]3)[CH:19]=[C:20]([C:22]#[CH:23])[CH:21]=2)[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7][CH:8]=1)#[N:2]

Participants

5

Reactant 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 86583542HCID 86583542, compound

Product 1

HCID 86583543HCID 86583543, compoundYield 24.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

130 mg of the ethyl (RS)-(4-cyano-phenylamino)-(3-pyrrolidin-1-ylmethyl-5-trimethylsilanylethynyl-phenyl)-acetate described in Example 156.4 were dissolved in 2 ml of THF and treated at 0° C. with 0.43 ml of a 1 molar solution of tetrabutylammonium fluoride in THF. After 5 hrs. at 0° C. water was added to the reaction mixture and an intermediate was extracted with ethyl acetate. This intermediate was treated at 0° C. in 5 ml of MeOH with 31 mg of sodium cyanoborohydride. Then, the pH was adjusted to 6 with methanolic HCl and the reaction mixture was stirred overnight at room temperature. The reaction mixture was then made basic with methanolic KHCO3 and, after removal of the solvent in a vacuum, the residue was purified by column chromatography (CH2Cl2/methanol). There were obtained 27 mg of ethyl (RS)-(4-cyano-phenylamino)-(3-ethynyl-5-pyrrolidin-1-ylmethyl-phenyl)-acetate as a light yellow solid; MS: 374 ([M+H]+).

Workup

  1. extractionan intermediate was extracted with ethyl acetate
  2. additionThis intermediate was treated at 0° C. in 5 ml of MeOH with 31 mg of sodium cyanoborohydride
  3. customafter removal of the solvent in a vacuum
  4. customthe residue was purified by column chromatography (CH2Cl2/methanol)

Sources & evidence

ORD record
ord-9c3cc1c73542489e92a76fcc35ada160
Source dataset
uspto-grants-2002_11
Patent number
US06476264B2

Reaction notes

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