Diisopropylamine → HCID 86633705, compound

HRID 887939Notes

Reaction equation

HRID 887939 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[OH:13][C@H:14]([CH3:20])[CH2:15][C:16]([O:18][CH3:19])=[O:17].[CH2:21](Br)[CH:22]=[CH:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[C:24]1(/[CH:23]=[CH:22]/[CH2:21][C@H:15]([C@H:14]([OH:13])[CH3:20])[C:16]([O:18][CH3:19])=[O:17])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 98116BromomethylstyreneHCID 2724279Methyl 3-hydroxybutyrate, (R)-HCID 178418339Butyllithium

Product 1

HCID 86633705HCID 86633705, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

To a solution of diisopropylamine (47.1 g, 466.1 mmol) in THF (500 mL) cooled to −50.degree. C. is added n-butyllithium (466.1 mmol, 2.5M in hexanes) and the resulting solution is stirred at −50.degree. C. for 0.5 h. The reaction mixture is cooled to −78.degree. C. followed by slow addition of methyl (3R)-3-hydroxybutanoate (25 g, 211.9 mmol). After 0.5 h a solution of cinnamyl bromide (45.9 g, 233.0 mmol) in HMPA (10 mL) is added and the reaction mixture is allowed to warm to 0.degree. C. and stirred for 16 h. The reaction mixture is quenched by addition 30 mL of saturated aqueous ammonium chloride solution, is poured into 400 mL of 1 M hydrochloric acid, and is extracted with two 500 mL portions of ethyl acetate. The combined organic layers are dried over magnesium sulfate, concentrated in vacuo, and purified by silica gel chromatography (elution with 25% ethyl acetate-hexanes) to afford methyl (2R,3R)-2-[(2E)-3-phenyl-2-propen-1-yl]-3-hydroxybutanoate as a yellow oil (42 g, 85% yield).

Workup

  1. temperatureThe reaction mixture is cooled to −78.degree
  2. temperatureto warm to 0.degree
  3. stirringand stirred for 16 h
  4. customThe reaction mixture is quenched by addition 30 mL of saturated aqueous ammonium chloride solution
  5. additionis poured into 400 mL of 1 M hydrochloric acid
  6. extractionis extracted with two 500 mL portions of ethyl acetate
  7. dry with materialThe combined organic layers are dried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. custompurified by silica gel chromatography (elution with 25% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-0850189e8acb46c784879edd5cdfc7cc
Source dataset
uspto-grants-2012_08
Patent number
US08247451B2

Reaction notes

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