Isobutyric Acid → 2,2-Dimethyl-6-[2-[4-(4-morpholinyl)phenyl]ethoxy]hexanoic acid

HRID 2166163Notes

Reaction equation

HRID 2166163 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([OH:18])(=[O:17])[CH:14]([CH3:16])[CH3:15].Br[CH2:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[CH:29][CH:28]=1>CCCCCC.C1COCC1>[CH3:15][C:14]([CH3:16])([CH2:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[CH:29][CH:28]=1)[C:13]([OH:18])=[O:17]

Participants

7

Reactant 4

HCID 6590Isobutyric AcidHCID 7912DiisopropylamineHCID 20062845HCID 20062845, compoundHCID 178418339Butyllithium

Product 1

HCID 200628192,2-Dimethyl-6-[2-[4-(4-morpholinyl)phenyl]ethoxy]hexanoic acidYield 99.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

n-Butyllithium in hexane (1.53M, 113.5 ml) was added dropwise to N,N-diisopropylamine (17.9 g) in THF (100 ml) at -78° under nitrogen. The mixture was warmed to 0°, stirred for 1 h and treated dropwise with isobutyric acid (7.65 g) in THF (20 ml). The resulting suspension was stirred at room temperature for 3 h, and the product of stage (ii) (20.0 g) was added dropwise. The reaction mixture was stirred for 16 h at room temperature and the solvent was evaporated. The resultant oil was partitioned between EA (250 ml) and water (250 ml). The aqueous layer was acidified to pH6 with 2N aqueous hydrochloric acid and the organic extract was separated. The aqueous layer was extracted with EA (250 ml) and the combined extracts were concentrated to leave the title compound as an orange oil (20.4 g). T.l.c. (ER) Rf 0.53.

Workup

  1. temperatureThe mixture was warmed to 0°
  2. stirringThe resulting suspension was stirred at room temperature for 3 h
  3. stirringThe reaction mixture was stirred for 16 h at room temperature
  4. customthe solvent was evaporated
  5. customThe resultant oil was partitioned between EA (250 ml) and water (250 ml)
  6. extractionthe organic extract
  7. customwas separated
  8. extractionThe aqueous layer was extracted with EA (250 ml)
  9. concentrationthe combined extracts were concentrated

Sources & evidence

ORD record
ord-45581d99449b4437aad845d3e2c788bb
Source dataset
uspto-grants-1990_07
Patent number
US04943591

Reaction notes

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