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

HRID 1197693ノート

反応式

HRID 1197693 の反応式
[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]

参加物

7

反応物 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

生成物 1

HCID 19373579N-(6-Cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)-a-hydroxybenzeneacetamide収率 110.4%

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-1f48206eea2b4e83922b14372b32d212
出典データセット
uspto-grants-1994_01
特許番号
US05276168

反応ノート

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