Dimethylformamide → HCID 68991024, compound

HRID 661119Notes

Reaction equation

HRID 661119 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-e9c32bfe0e6b445a9dc2ff5e03fd2d50
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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