Hydrochloric Acid → 1-(3,4-Dimethoxyphenyl)-2-carboxy-6-cyano-6-(i-propyl)-6-(3,4-dimethoxyphenyl)hexane

HRID 65307

Reaction equation

HRID 65307 reaction equation
C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH2:29][CH2:30][C:31]([OH:33])=[O:32])[CH:24]=[CH:25][C:26]=1[O:27][CH3:28].[CH3:34][O:35][C:36]1[CH:37]=[C:38]([C:44]([CH:51]([CH3:53])[CH3:52])([CH2:47][CH2:48][CH2:49]Cl)[C:45]#[N:46])[CH:39]=[CH:40][C:41]=1[O:42][CH3:43].Cl>C1COCC1.O.CN(C)P(N(C)C)(N(C)C)=O>[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH2:29][CH:30]([C:31]([OH:33])=[O:32])[CH2:49][CH2:48][CH2:47][C:44]([C:45]#[N:46])([CH:51]([CH3:52])[CH3:53])[C:38]2[CH:39]=[CH:40][C:41]([O:42][CH3:43])=[C:36]([O:35][CH3:34])[CH:37]=2)[CH:24]=[CH:25][C:26]=1[O:27][CH3:28]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 8058HexaneHCID 750193-(3,4-Dimethoxyphenyl)propionic acidHCID 6199535-Chloro-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrileHCID 178418339Butyllithium

Product 1

HCID 140271651-(3,4-Dimethoxyphenyl)-2-carboxy-6-cyano-6-(i-propyl)-6-(3,4-dimethoxyphenyl)hexaneYield 91.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Procedure

A 1.6M solution of n-butyllithium in hexane (91.8 mL, 147 mmol) was added to a -20° C. solution of diisopropylamine (21 mL, 150 mmol) in THF (480 mL). Hexamethylphosphoramide (56 mL) was added and the mixture maintained at -20° C. while a solution of 3-(3,4-dimethoxyphenyl)propionic acid (15.1 g, 72 mmol) in THF (75 mL) was added. The resulting solution was stirred at room temperature for one hour, and then cooled to -50° C. A solution of 2-(3,4-dimethoxyphenyl)-2-isopropyl-2-(3-iodopropyl)acetonitrile (22, 27.9 g, 72 mmol) was added, and the mixture allowed to warm to room temperature while stirring for 12 hours. The resulting mixture was added to water, acidified with HCl, and extracted three times with ether. The organic layer was washed with aqueous Na2SO3 and brine, dried over Na2SO4, and evaporated to yield 1-(3,4-dimethoxyphenyl)-2-carboxy-6-cyano-6-(i-propyl)-6-(3,4-dimethoxyphenyl)hexane (23, 31 g) as a thick oil.

Workup

  1. additionwas added
  2. temperaturecooled to -50° C
  3. temperatureto warm to room temperature
  4. stirringwhile stirring for 12 hours
  5. extractionextracted three times with ether
  6. washThe organic layer was washed with aqueous Na2SO3 and brine
  7. dry with materialdried over Na2SO4
  8. customevaporated

Sources & evidence

ORD record
ord-f6b0a2b1d9cd4045ad331bd44de0eb99
Source dataset
uspto-grants-1986_09
Patent number
US04613606

Linked notes

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