Dimethylformamide → HCID 68991024, compound

HRID 2109790Notes

Reaction equation

HRID 2109790 reaction equation
[C:1]([O:5][C:6]([CH:8]([CH:14]([OH:25])[C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C=O)C.[CH3:31][O:32][CH2:33]Cl.C(N(CC)C(C)C)(C)C>ClCCCl.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:1]([O:5][C:6]([CH:8]([CH:14]([O:25][CH2:31][O:32][CH3:33])[C:15]1[CH:16]=[CH:17][C:18]([C:21]([F:23])([F:24])[F:22])=[CH:19][CH:20]=1)[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 68990291HCID 68990291, compound

Product 1

HCID 68991024HCID 68991024, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of ethyl 2-(tert-butoxycarbonyl)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propanoate (9.25 g, 24.5 mmol) in DMF (3.78 mL, 49.0 mmol) and 1,2-dichloroethane (20 mL) was added tetra-n-butylammonium iodide (9.51 g, 25.7 mmol), chloromethyl methyl ether (5.59 mL, 73.5 mmol) and N,N-diisopropylethylamine (12.8 mL, 73.5 mmol). The mixture was gradually heated to 45° C. and stirred overnight. The crude product was concentrated in vacuo, diluted with CH2Cl2 and washed three times with water. The organic phase was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography: 16%-20%-25% EtOAc-Hexane. The product was obtained as a white solid. LCMS (API-ES) m/z (%): 322 (M+1−100).

Workup

  1. concentrationThe crude product was concentrated in vacuo
  2. additiondiluted with CH2Cl2
  3. washwashed three times with water
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel chromatography
  7. customThe product was obtained as a white solid

Sources & evidence

ORD record
ord-6481d84a5c68426cb1c883c991ed1f58
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

Loading…