Diethyl Ether → 2-[2-(3-Bromo-phenyl)-2-hydroxy-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester

HRID 221716Notes

Reaction equation

HRID 221716 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C:4]([O:10][CH2:11][C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[CH:15]=1)=[O:13])([CH3:9])[C:5]([F:8])([F:7])[F:6].[CH3:22][Al](C)C.CCCCCCC.[Li]C.CCOCC>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:21])[C:4]([O:10][CH2:11][C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Br:20])[CH:15]=1)([OH:13])[CH3:22])([CH3:9])[C:5]([F:8])([F:6])[F:7]

Participants

7

Reactant 5

HCID 3283Diethyl EtherHCID 8900HeptaneHCID 16682925TrimethylaluminumHCID 666655732-[2-(3-Bromo-phenyl)-2-oxo-ethoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl esterHCID 178418348HCID 178418348, compound

Product 1

HCID 666655182-[2-(3-Bromo-phenyl)-2-hydroxy-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-[2-(3-bromo-phenyl)-2-oxo-ethoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester (6.6 g, 17 mmol) in toluene (120 ml) was added under argon at −78° C. a 2M solution of AlMe3 in heptane (17 ml, 34 mmol) and after stirring for 0.5 h at −78° C. a 1.6 M solution of MeLi in Et2O (21.3 ml, 34 mmol) over a period of 40 min. After stirring for 0.5 h at −78° C. the reaction mixture was added to a cold aqueous NaH2PO4 solution and was extracted with EtOAc. Combined organic layers were washed with brine, dried over MgSO4, filtered and evaporated. The crude product was purified by flash-chromatography on silica gel (toluene to toluene/EtOAc 10:1) to provide a diastereomeric mixture of the title compound as a yellow oil: TLC (toluene/EtOAc 10:1): Rf=0.34 and 0.37; HPLC RtH5=1.359 min; 1H NMR (360 MHz, CDCl3): δ 7.69 (m, 1H), 7.43 (m, 2H), 7.25 (t, 1H), 3.86 (s, 3H), 3.68 (m, 2H), 3.43 and 3.33 (s, 1H), 1.63 and 1.61 (s, 3H), 1.58 (s, 3H); ESIMS: 402, 404 [(M+NH4)+].

Workup

  1. extractionwas extracted with EtOAc
  2. washCombined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified by flash-chromatography on silica gel (toluene to toluene/EtOAc 10:1)
  7. customto provide

Sources & evidence

ORD record
ord-1d0769c505ba475787fa0d1bd43653d4
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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