Ethyl Acetate → 4-[2-(4-Bromo-phenyl)-2-methoxycarbonyl-ethyl]-benzoic acid tert-butyl ester

HRID 1401891Notes

Reaction equation

HRID 1401891 reaction equation
C(O[C:5]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][C:6]=1C)(=O)C.[C:13]([O:17][C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([CH2:25]I)=[CH:21][CH:20]=1)([CH3:16])([CH3:15])[CH3:14].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[C:38]([O:41][CH2:42]C)(=[O:40])[CH3:39]>C1COCC1.O>[C:13]([O:17][C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH:39]([C:5]2[CH:6]=[CH:7][C:8]([Br:11])=[CH:9][CH:10]=2)[C:38]([O:41][CH3:42])=[O:40])=[CH:21][CH:20]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 2733832Lithium HexamethyldisilazideHCID 600267744-Bromo-2-methylphenyl acetateHCID 672121184-Iodomethyl benzoic acid tert-butyl ester

Product 1

HCID 672113474-[2-(4-Bromo-phenyl)-2-methoxycarbonyl-ethyl]-benzoic acid tert-butyl esterYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 246.63 g of methyl-4-bromophenyl acetate and 342.54 g of 4-Iodomethyl benzoic acid tert-butyl ester in THF (1233 mL) was cooled to −8° C. A solution of lithium hexamethyl disilazide in THF (1185 mL, 1.0 M) was added dropwise ensuring that the temperature remaine below −2° C. After the addition was complete, the reaction was allowed to proceed for ˜45 min at the same temperature and then poured over a stirring mixture of ethyl acetate (2.46 L) and water (1.23 L). The organic phase was washed with saturated ammonium chloride and then with water. Dried over magnesium sulfate and concentrated under reduced pressure to obtain 450.5 g (100% yield) thick oil. HNMR: CDCl3, 1.41 (s, 9H), 2.88-2.90 (m, 1H), 3.24-3.28 (m, 1H), 3.45 (s, 3H), 3.63 (t, 1H). 6.96-6.99 (m, 4H), 7.25 (d, 2H), 7.68 (d, 2H)

Workup

  1. customremaine below −2° C
  2. additionAfter the addition
  3. washThe organic phase was washed with saturated ammonium chloride
  4. dry with materialDried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6d779bdda11245fc89438c93af105045
Source dataset
uspto-grants-2014_12
Patent number
US08907103B2

Reaction notes

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