Diisopropylamine → HCID 18434225, compound

HRID 1636748Notes

Reaction equation

HRID 1636748 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([N:16]([CH3:32])[CH2:17]/[CH:18]=[CH:19]/[CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28](=[O:30])[CH3:29])=[CH:24][C:23]=1[F:31])[CH:14]=[CH2:15].[CH3:33][C:34]([CH3:38])=[CH:35][CH:36]=[O:37].C(=O)(O)[O-].[Na+]>C1COCC1.CCCCCC.CCOCC.C(Cl)Cl.C(O)(=O)C>[CH2:13]([N:16]([CH3:32])[CH2:17]/[CH:18]=[CH:19]/[CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28](=[O:30])[CH2:29][CH:36]([OH:37])[CH:35]=[C:34]([CH3:38])[CH3:33])=[CH:24][C:23]=1[F:31])[CH:14]=[CH2:15]

Participants

11

Reactant 5

HCID 7912DiisopropylamineHCID 610203-Methyl-2-butenalHCID 516892Sodium BicarbonateHCID 18434339HCID 18434339, compoundHCID 178418339Butyllithium

Product 1

HCID 18434225HCID 18434225, compound

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 0.86 ml of diisopropylamine in 5 ml of THF is treated dropwise at 0° C. with 3.5 ml of 1.6M butyllithium in hexane. After 15 min. the mixture is cooled to -78° C. and 1.1 g of (E)-1-[4-[4-(allyl-methyl-amino)-but-2-enyloxy]-3-fluoro-phenyl]-ethanone (Ex. Fa) in 3.9 ml of THF is added dropwise. After 1 hr. at -78° C. 0.7 ml of 3-methyl-2-butenal in 0.8 ml of THF is added dropwise. After 20 min. at -78° C. 0.86 ml of acetic acid in 4.6 ml of ether is added dropwise and the mixture is poured into saturated sodium bicarbonate solution/methylene chloride. The organic phase is dried and evaporated. After silica gel chromatography with (97.5%) methylene chloride/methanol the residue is dissolved in ethanol with 0.24 g of fumaric acid, evaporated and precipitated from methylene chloride with ethyl acetate/ether. There is obtained 0.64 g of (E)-(RS)-1-[4-[4-(allyl-methyl-amino)-but-2-enyloxy]-3-fluoro-phenyl]-3-hydroxy-5-methyl-hex-4-en-1-one.fumarate (1:1), MS: m/e 362 (M+H+).

Workup

  1. customat -78° C
  2. waitAfter 20 min. at -78° C
  3. customThe organic phase is dried
  4. customevaporated
  5. dissolutionAfter silica gel chromatography with (97.5%) methylene chloride/methanol the residue is dissolved in ethanol with 0.24 g of fumaric acid
  6. customevaporated
  7. customprecipitated from methylene chloride with ethyl acetate/ether

Sources & evidence

ORD record
ord-d57ac53aa70840f6a1f6c0004e6de46e
Source dataset
uspto-grants-2000_03
Patent number
US06034275

Reaction notes

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