Hydrochloric Acid → N-(6-Cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-a-hydroxybenzeneacetamide

HRID 1197693

Reaktionsgleichung

Reaktionsgleichung von HRID 1197693
[CH:1]1[CH:6]=[CH:5][C:4]([C@@H:7]([OH:11])[C:8]([OH:10])=O)=[CH:3][CH:2]=1.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[C:30]([C:32]1[CH:33]=[CH:34][C:35]2[O:40][C:39]([CH3:42])([CH3:41])[CH2:38][CH:37]([NH:43]C(NC3C=CC=CC=3)=O)[C:36]=2[CH:53]=1)#[N:31].CN(C)CCCCCN=C=N.Cl>>[C:30]([C:32]1[CH:33]=[CH:34][C:35]2[O:40][C:39]([CH3:42])([CH3:41])[CH2:38][CH:37]([NH:43][C:8](=[O:10])[CH:7]([OH:11])[C:4]3[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=3)[C:36]=2[CH:53]=1)#[N:31]

Komponenten

7

Edukt 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 11914(-)-Mandelic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 9973362N-(6-Cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-N'-phenylureaHCID 536288631-(3-Dimethylaminopropyl)-2-ethylcarbodiimide

Produkt 1

HCID 19373579N-(6-Cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-a-hydroxybenzeneacetamideAusbeute 110,4 %

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of R-(-)-mandelic acid (22.1 g, 0.14 mole) and 1-hydroxy-benzotriazole hydrate (19.6 g, 0.14 mole) cooled to 0° C. was added successively N-methylmorpholine (16.2 g, 0.16 mole), 4-amino-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran (29.4g, 0.14 mole, from Example 8, part D) and 1-(3-dimethylaminopropyl)-2-ethylcarbodiimide.HCl (27.9 g, 0.14 mole). The reaction mixture was stirred 0.5 hours at 0° C. and two hours at room temperature. The solvent was recovered under vacuum and the residue was partitioned between 5% aqueous HCl and ethyl acetate. The organic fraction was washed with saturated sodium bicarbonate solution, saturated sodium chloride solution, dried over magnesium sulfate and evaporated in vacuo to obtain 52 g of yellow gum. The crude diastereomer mixture was chromatographed on silica eluting with 1:1 hexane/ethyl acetate to obtain 19.8 g (40.6%) of Isomer B (isomer A being subject of Example 19, part A); m.p.=135-136° C., [α]D25 =-60.8°. 1H NMR (CDCl3) δ 7.51-7.30 (m, 6H), 7.27 (d, J=1.76 Hz, 1H), 6.80 (m, 2H), 5.18 (m, 1H), 5.08 (d, J=2.93 Hz, 1H), 3.97 (d, J=2.93 Hz, 1H), 2.12 (dd, J=6.15 and 13.19 Hz, 1H), 1.69 (dd, J=11.43 and 13.20 Hz, 1H), 1.40 (s, 3H), 1.30 (s, 3H); 13C NMR (CDCl3) δ 172.59, 157.53, 139.13, 133.07, 132.81, 131.98, 128.92, 126.38, 122.86, 118.97, 118.56, 103.25, 76.83, 74.26, 41.81, 38.96, 29.15, 24.62; MS: (M+H)+ @337.

Aufarbeitung

  1. customThe solvent was recovered under vacuum
  2. customthe residue was partitioned between 5% aqueous HCl and ethyl acetate
  3. washThe organic fraction was washed with saturated sodium bicarbonate solution, saturated sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-1f48206eea2b4e83922b14372b32d212
Quelldatensatz
uspto-grants-1994_01
Patentnummer
US05276168

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