Ethyl Acetate → {4-[3-(2-Cyano-pyrimidin-4-yloxy)-phenoxymethyl]-benzyl}carbamic acid tert-butyl ester

HRID 643511Notes

Reaction equation

HRID 643511 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26](Cl)[N:25]=3)[CH:18]=2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C1N2CC[N:34](CC2)[CH2:33]1.[C-]#N.[K+].CCOC(C)=O>CS(C)=O.O>[C:1]([O:5][C:6](=[O:31])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([C:33]#[N:34])[N:25]=3)[CH:18]=2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 9032Potassium CyanideHCID 9237Dabco2×HCID 86622897{4-[3-(2-Chloro-pyrimidin-4-yloxy)-phenoxymethyl]-benzyl}carbamic acid tert-butyl ester

Product 1

HCID 68579046{4-[3-(2-Cyano-pyrimidin-4-yloxy)-phenoxymethyl]-benzyl}carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 23503278(Methanesulfinyl)methane--water (1/1)Solvent

Procedure

{4-[3-(2-Chloro-pyrimidin-4-yloxy)-phenoxymethyl]-benzyl}carbamic acid tert-butyl ester (126 mg; 0.285 mmol; Stage 5.2), DABCO (16 mg; 0.143 mmol) and KCN (38 mg; 0.584 mmol) are dissolved in DMSO/water 4:1 (4 mL) at rt under an atmosphere of argon. After 20 min, more DABCO (16 mg) is added and the reaction is continued for a total of 1 h 50 min. The reaction mixture is poured onto brine, taken up into EtOAc, washed with water and brine and dried (Na2SO4). After filtration, the solvent is removed under reduced pressure and the crude product is purified by flash chromatography over silica gel (eluting with Hexane/EtOAc 80:20) to give the title compound of Stage 5.3 as an oil; ES-MS: [M−H]−; m/z=431; Rf (Hexane/EtOAc 1:1)=0.45; HPLC: AtRet=5.19 min.

Workup

  1. customis continued for a total of 1 h 50 min
  2. additionThe reaction mixture is poured onto brine
  3. washwashed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationAfter filtration
  6. customthe solvent is removed under reduced pressure
  7. customthe crude product is purified by flash chromatography over silica gel (eluting with Hexane/EtOAc 80:20)

Sources & evidence

ORD record
ord-e3c8029a486b4cc7a4b8b09abcfbcc89
Source dataset
uspto-grants-2010_04
Patent number
US07700605B2

Reaction notes

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