Benzenecarboximidic acid, ethyl ester, hydrochloride (1:1) → HCID 178495957、化合物

HRID 353334

反応式

HRID 353334 の反応式
Cl.[C:2](=[NH:12])(OCC)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:13][O:14][CH:15]([O:18][CH3:19])[CH2:16][NH2:17]>CO.[OH-].[Na+]>[CH3:13][O:14][CH:15]([O:18][CH3:19])[CH2:16][NH:17][C:2](=[NH:12])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

参加物

5

反応物 2

HCID 79249Benzenecarboximidic acid, ethyl ester, hydrochloride (1:1)HCID 89728Aminoacetaldehyde dimethyl acetal

生成物 1

HCID 178495957HCID 178495957、化合物収率 104.5%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒2 回HCID 14798Sodium Hydroxide溶媒

実験手順

(EX-1A) A solution of ethyl benzimidate hydrochloride (92.25 g, 496.9 mmol) in 300.0 mL dry methanol (1.68 M) was cooled to ca 0° C. and added a solution of aminoacetaldehyde dimethyl acetal (73.10 mL, 670.9 mmol) in dry methanol (75.0 mL, 9.0 M) drop wise at such a rate the temperature was kept below 5° C. The resulting solution was allowed to stir for 3 days with the temperature being maintained below 5° C. The reaction mixture was then concentrated under reduced pressure to give a yellow oil. The residue was dissolved in 1 N NaOH (750 mL) and extracted with dichloromethane (4×250 mL). The organic solutions were combined, dried (MgSO4), and concentrated to give 108.13 g crude N-(2,2-dimethoxyethyl)benzamidine as a yellow oil. The crude N-(2,2-dimethoxyethyl)benzamidine (108.13 g, 519.2 mmol) in dry methanol (125.0 mL, 4.2 M) was added dimethyl methoxymethylenemalonate (94.13 g, 540.5 mmol) in one portion at room temperature. The resulting mixture was heated to approximately 100° C., where the solvent was slowly distilled off over a two hour period. The resulting dark brown solution was allowed to cool to room temperature and was diluted ethyl acetate (1 L). The organic solution was washed with saturated NH4Cl (2×500 mL) and brine 1×500 ml). The organic solution was dried (MgSO4), filtered and concentrated. Purification of the crude product by MPLC (25% ethyl acetate/hexane) gave pure methyl 1-(2,2-dimethoxyethyl-2-phenylpyrimidin-6(1H)-one-5-carboxylate (EX-1A) in 73% yield as a tan oil: 1H NMR (300 MHz, CDCl3) δ 8.73 (s, 1H), 7.59-7.49 (m, 5H), 4.86 (t, J=5.5 Hz, 1H), 4.16 (d, J=5.4 Hz, 2H), 3.95 (s, 3H), 3.32 (s, 6H); 13CNMR (75 Hz, CDCl3) δ 165.9, 164.6, 159.3, 158.2, 134.6, 130.9, 128.93, 128.78, 114.9, 101.4, 56.0, 55.1, 52.7, 49.1; HRMS (ES) calcd for C16H19N2O5 319.1294, found 319.1288.

後処理

  1. customwas kept below 5° C
  2. temperaturebeing maintained below 5° C
  3. concentrationThe reaction mixture was then concentrated under reduced pressure
  4. customto give a yellow oil
  5. extractionextracted with dichloromethane (4×250 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-0b13027f06fe4037a56c6e35edbce19b
出典データセット
uspto-grants-2004_06
特許番号
US06750342B1

関連ノート

読み込み中…