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

HRID 538183노트

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HRID 538183 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
23 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-69a23b2054714cc6b7642f912aee57a3
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865713B2

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