Ethyl isobutyrate → Ethyl 6-bromo-2,2-dimethylhexanoate

HRID 845471Notes

Reaction equation

HRID 845471 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([O:18][CH2:19][CH3:20])(=[O:17])[CH:14]([CH3:16])[CH3:15].[Br:21][CH2:22][CH2:23][CH2:24][CH2:25]Br>CCCCCC.O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O>[CH3:15][C:14]([CH3:16])([CH2:25][CH2:24][CH2:23][CH2:22][Br:21])[C:13]([O:18][CH2:19][CH3:20])=[O:17]

Participants

8

Reactant 4

HCID 7342Ethyl isobutyrateHCID 7912DiisopropylamineHCID 80561,4-DibromobutaneHCID 178418339Butyllithium

Product 1

HCID 10444833Ethyl 6-bromo-2,2-dimethylhexanoate

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-70 °C

Procedure

A solution of n-butyllithium (1.6M, 63 ml, 0.10 mol.) in hexane was added dropwise to a solution of diisopropylamine (10.1 g, 0.10 mol.) in anhydrous tetrahydrofuran (100 ml) at -50° C. The mixture was stirred for 0.5 hours and cooled to -70° C. A solution of ethyl isobutyrate (12.2 g, 0.105 mol.) in tetrahydrofuran (20 ml) was then added and the resulting mixture was stirred at -70° C. for 1 hour. 1,4-Dibromobutane (30.4 g, 0.14 mol) was then added, followed by hexamethylphosphoramide (30 g). The mixture was maintained at -70° C. for 0.5 hours and then warmed to room temperature over 1 hour. The solvent was evaporated off under reduced pressure, treated with an excess of an aqueous saturated solution of ammonium chloride (500 ml) and extracted with ethyl acetate (2×150 ml). The combined extracts were washed with water (100 ml), hydrochloric acid (1N, 2×100 ml) aqueous saturated sodium hydrogen carbonate solution (100 ml) and dried (MgSO4). The solvent was evaporated off under reduced pressure and the residue was distilled to give ethyl 2,2-dimethyl-6-bromohexanoate as a pale yellow oil, (b.p. 73° C., 0.06 mm Hg).

Workup

  1. stirringthe resulting mixture was stirred at -70° C. for 1 hour
  2. temperatureThe mixture was maintained at -70° C. for 0.5 hours
  3. temperaturewarmed to room temperature over 1 hour
  4. customThe solvent was evaporated off under reduced pressure
  5. additiontreated with an excess of an aqueous saturated solution of ammonium chloride (500 ml)
  6. extractionextracted with ethyl acetate (2×150 ml)
  7. washThe combined extracts were washed with water (100 ml), hydrochloric acid (1N, 2×100 ml) aqueous saturated sodium hydrogen carbonate solution (100 ml)
  8. dry with materialdried (MgSO4)
  9. customThe solvent was evaporated off under reduced pressure
  10. distillationthe residue was distilled

Sources & evidence

ORD record
ord-bdda01e1ba1c4415983dfdf550d33eec
Source dataset
uspto-grants-1988_07
Patent number
US04758573

Reaction notes

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