Ethyl Acetate → 6-(Hydroxymethyl)-2-methoxy-4-methylnicotinonitrile

HRID 62395

Reaktionsgleichung

Reaktionsgleichung von HRID 62395
[C:1]([C:3]1[C:4]([CH3:16])=[CH:5][C:6]([C:11](OCC)=[O:12])=[N:7][C:8]=1[O:9][CH3:10])#[N:2].[Cl-].[Ca+2].[Cl-].[BH4-].[Na+].CCOC(C)=O>O1CCCC1.C(O)C.C(Cl)Cl>[OH:12][CH2:11][C:6]1[CH:5]=[C:4]([CH3:16])[C:3]([C:1]#[N:2])=[C:8]([O:9][CH3:10])[N:7]=1

Komponenten

8

Edukt 4

HCID 8857Ethyl Acetate2×HCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 67466404Ethyl 5-cyano-6-methoxy-4-methylpicolinate

Produkt 1

HCID 674676336-(Hydroxymethyl)-2-methoxy-4-methylnicotinonitrileAusbeute 93 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a stirred suspension of ethyl 5-cyano-6-methoxy-4-methylpicolinate (5.0 g, 22.70 mmol) and calcium chloride (10 g, 90 mmol) in tetrahydrofuran (50 mL) and ethanol (50.0 mL) at 0° C. in an ice bath was added sodium borohydride (2.5 g, 66.1 mmol). The reaction was slowly allowed to warm to RT and stirred for 18 hr. A large amount of ppt. formed and LCMS showed that the reaction was complete. An equal volume of EtOAc was added and the reaction stirred for 1 hr. The suspension was filtered through a pad of Celite and washed with EtOAc. The filtrate was transferred to a separatory funnel, washed with aq. NH4Cl, brine, dried (Na2SO4), filtered and concentrated under vacuum. Purification by silica gel chromatography (Analogix, SF40-120 g, 0 to 30% EtOAc in CH2Cl2) gave the product 6-(hydroxymethyl)-2-methoxy-4-methylnicotinonitrile (3.75 g, 21.05 mmol, 93% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.16 (s, 1H), 5.61 (t, J=5.8 Hz, 1H), 4.51 (d, J=5.8 Hz, 2H), 3.94 (s, 3H), 2.47 (s, 3H). MS(ES)+ m/e 179.1 [M+H]+.

Aufarbeitung

  1. customformed
  2. stirringthe reaction stirred for 1 hr
  3. filtrationThe suspension was filtered through a pad of Celite
  4. washwashed with EtOAc
  5. customThe filtrate was transferred to a separatory funnel
  6. washwashed with aq. NH4Cl, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customPurification by silica gel chromatography (Analogix

Quellen und Nachweise

ORD-Eintrag
ord-f71152a941184a6f8c20dc1296e62042
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09446041B2

Verknüpfte Notizen

Wird geladen…