Iopanoic Acid → Methyl 2-cyanomethyl-2-phenylmethylbutanoate

HRID 1108366

Reaktionsgleichung

Reaktionsgleichung von HRID 1108366
[C:1]1([CH2:7][CH:8]([CH2:13][CH3:14])[C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:16][C:17]#[N:18].C([N-]C(C)C)(C)C.[Li+].CN(P(N(C)C)(N(C)C)=O)C.CCC(C(O)=O)CC1C(I)=CC(I)=C(N)C=1I>C1COCC1>[C:1]1([CH2:7][CH:8]([CH2:13][CH3:14])[C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:17]([CH2:16][C:8]([CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([CH2:13][CH3:14])[C:9]([O:11][CH3:12])=[O:10])#[N:18]

Komponenten

8

Edukt 5

HCID 3735Iopanoic AcidHCID 11534BromoacetonitrileHCID 12679HexamethylphosphoramideHCID 2724682Lithium diisopropylamideHCID 12647073Methyl 2-phenylmethylbutyrate

Produkt 2

HCID 10609559Methyl 2-cyanomethyl-2-phenylmethylbutanoateAusbeute 103,4 %HCID 12647073Methyl 2-phenylmethylbutyrate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Methyl 2-phenylmethylbutyrate (9.60 g, 50 mmol) was reacted with bromoacetonitrile (7.20 g, 60 mmol) in the presence of lithium diisopropylamide in THF (150 mL) and HMPA (4.3 mL, 25 mmol), as described above in the preparation of Example 4, to give 12.08 g of the crude product as a dark colored liquid. Methyl 2-phenylmethylbutyrate was prepared as in Colombo M, De Amici M, De Micheli C, Pitre D, Carrea G, Riva S (1991) "Chemoenzymatic synthesis of the enantiomers of iopanic acid" Tetrahedron:Asymmetry, 2, 1021-1030. Column chromatography over silica gel (hexanes-CH2Cl2, 3:2) afforded 5.98 g (52%) of the nitrile as a colorless viscous liquid. Analytical sample was prepared by bulb-to-bulb distillation (pot temp. 105° C. (0.5 mmHg)). Lithium diisopropylamide was prepared by treating diisopropylamine (5.56 g, 55 mmol) with butyllithium in hexanes (2.5 M, 22 mL, 55 mmol).

Aufarbeitung

  1. customas described above in the preparation of Example 4
  2. customto give 12.08 g of the crude product as a dark colored liquid

Quellen und Nachweise

ORD-Eintrag
ord-9b11bd59a46b4a20a4f6931baf252a2c
Quelldatensatz
uspto-grants-2000_05
Patentnummer
US06066666

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