Hydrochloric Acid → [2-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-5-yl]-methanol

HRID 538183ノート

反応式

HRID 538183 の反応式
C[O:2][C:3]([C:5]1[CH:20]=[CH:19][C:8]2[N:9]([CH2:13][O:14][CH2:15][CH2:16][O:17][CH3:18])[C:10]([Cl:12])=[N:11][C:7]=2[CH:6]=1)=O.C1(NC(C2C=CC3NC(N4C=C(C(O)=O)C=N4)=NC=3C=2)=O)C=CC=CC=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl>O.C1COCC1>[Cl:12][C:10]1[N:9]([CH2:13][O:14][CH2:15][CH2:16][O:17][CH3:18])[C:8]2[CH:19]=[CH:20][C:5]([CH2:3][OH:2])=[CH:6][C:7]=2[N:11]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 21226445Aluminium lithium hydrideHCID 669372622-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazole-5-carboxylic acid methyl esterHCID 1785248161-(5-phenylcarbamoyl-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid

生成物 1

HCID 66937356[2-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazol-5-yl]-methanol収率 78.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
23 °C

実験手順

To a stirred solution of 2-chloro-1-(2-methoxy-ethoxymethyl)-1H-benzoimidazole-5-carboxylic acid methyl ester (Intermediate from EXAMPLE 120, product of Step C) (0.500 g, 1.67 mmol) and THF (30 mL) was added lithium aluminum hydride (2M in THF, 0.836 mL) dropwise over 10 min at 0° C. The reaction mixture was stirred for 48 h, warming to 23° C. The reaction mixture was cooled to 0° C., water (20 mL) was added and the resulting mixture was acidified with 1M HCl. The product was extracted with EtOAc (3×40 mL) and the combined organic layers were washed with brine, dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (5-80% EtOAc/hexanes) to yield the titled compound (0.356 g, 78%) as a 1:1 mixture of regioisomers. MS (ESI/CI): mass calcd. for C12H15ClN2O3, 270.1; m/z found, 271.1 [M+H]+. 1H (600 MHz, CDCl3): 7.65-7.61 (m, 2H), 7.52 (s, J=0.7 Hz, 1H), 7.45 (d, J=8.3 Hz, 1H), 7.35 (dd, J=8.3 Hz, 1.5 Hz, 1H), 7.27 (dd, J=8.2 Hz, 1.5 Hz, 1H), 5.63 (s, 2H), 5.62 (s, 2H), 4.81 (s, 2H), 4.77 (s, 2H), 3.64-3.60 (m, 4H), 3.49 (dd, J=5.4 Hz, 3.6 Hz, 4H), 3.35 (s, 3H), 3.34 (s, 3H), 2.59 (s, 1H), 2.50 (s, 1H).

後処理

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. extractionThe product was extracted with EtOAc (3×40 mL)
  3. washthe combined organic layers were washed with brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified (FCC) (5-80% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-69a23b2054714cc6b7642f912aee57a3
出典データセット
uspto-grants-2014_10
特許番号
US08865713B2

反応ノート

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