Triethylamine → 3,5-Bis(1,1-dimethylethyl)-2-hydroxybenzenecarboxamide

HRID 547986

Reaktionsgleichung

Reaktionsgleichung von HRID 547986
S(Cl)(Cl)=O.[CH3:5][C:6]([C:9]1[C:10]([OH:22])=[C:11]([CH:15]=[C:16]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:17]=1)[C:12](O)=[O:13])([CH3:8])[CH3:7].[C@H]1(N)CCCC[C@@H]1[NH2:29].C(N(CC)CC)C>CN(C)C=O.C1(C)C=CC=CC=1.O1CCCC1>[CH3:5][C:6]([C:9]1[C:10]([OH:22])=[C:11]([C:12]([NH2:29])=[O:13])[CH:15]=[C:16]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:17]=1)([CH3:8])[CH3:7]

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 882083,5-Bis(1,1-dimethylethyl)-2-hydroxybenzoic acid2×HCID 4793071,2-Diaminocyclohexane, (+)-

Produkt 1

HCID 193744503,5-Bis(1,1-dimethylethyl)-2-hydroxybenzenecarboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 1140TolueneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

Thionyl chloride (5.95 g, 50 mmol) was added to a mixture of 3,5-bis(1,1-dimethylethyl)-2-hydroxybenzoic acid (alternatively named 3,5-di-tert-butylsalicylic acid) (2.50 g, 10 mmol) and N,N-dimethylformamide (10 drops) in dry toluene (50 mL) at 60° C. After 1 hour at 60° C., the light yellow solution was evaporated in vacuo to leave a thick oil and then diluted with dry tetrahydrofuran (THF) (40 mL). After heating to 50° C., a solution of (1S,2S)-(+)-1,2-cyclohexanediamine (0.560, 4.90 mmol) in 10 mL of dry THF was added followed by triethylamine (1.01 g, 10 mmol). After 1 h at 50° C., the reaction mixture was quenched with water (25 mL) and then poured into ethyl acetate/water. The organic phase was separated, and the aqueous phase extracted with additional ethyl acetate (35 mL). The combined organic phase was washed once more with water and then evaporated onto silica gel. Purification by flash chromatography (hexanes-ethyl acetate, 0 to 20% ethyl acetate over 1 hour) and evaporation of the chromatography solvent in vacuo afforded the product as a foamy off-white solid (1.18 g). The product was further purified by stirring the white solid in methanol (5 mL) and then decanting the mother liquor from a small amount of insoluble, gummy solids. Evaporation of the methanol mother liquor afforded the title product as an off-white solid (1.15 g). 1H NMR (CDCl3) δ 1.29 (s, 18H), 1.38 (s, 18H), 1.82 (s, 2H), 2.22 (br s, 2H), 3.96 (br s, 2H), 6.95 (br s, 2H), 7.16 (d, J=2 Hz, 2H), 7.41 (d, J=2 Hz, 2H), 12.70 (s, 2H). MS ESI Positive: 579 (M+1), ESI Negative: 577 (M−1).

Aufarbeitung

  1. customthe light yellow solution was evaporated in vacuo
  2. customto leave a thick oil
  3. waitAfter 1 h at 50° C.
  4. customthe reaction mixture was quenched with water (25 mL)
  5. additionpoured into ethyl acetate/water
  6. customThe organic phase was separated
  7. extractionthe aqueous phase extracted with additional ethyl acetate (35 mL)
  8. washThe combined organic phase was washed once more with water
  9. customevaporated onto silica gel
  10. customPurification
  11. customby flash chromatography (hexanes-ethyl acetate, 0 to 20% ethyl acetate over 1 hour) and evaporation of the chromatography solvent in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-1ddc85c89b304a1b9d53793758214815
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07939685B2

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