Lithium Hydroxide → (S)-3-(1-methyl-1H-imidazol-5-yl)-3-(4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl)propanoic acid

HRID 2246655노트

반응식

HRID 2246655 반응식
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:15]2[N:19]([CH3:20])[CH:18]=[N:17][CH:16]=2)[CH2:9][C:10]([O:12]CC)=[O:11])=[CH:4][CH:3]=1.Br[CH2:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[C:29]([CH3:34])([CH3:33])[CH2:28][CH2:27][C:26]2([CH3:36])[CH3:35].C(=O)([O-])[O-].[Cs+].[Cs+].[Li+].[OH-]>CN(C=O)C.O>[CH3:20][N:19]1[C:15]([C@H:8]([C:5]2[CH:4]=[CH:3][C:2]([O:1][CH2:22][C:23]3[CH:32]=[CH:31][C:30]4[C:29]([CH3:34])([CH3:33])[CH2:28][CH2:27][C:26]([CH3:36])([CH3:35])[C:25]=4[CH:24]=3)=[CH:7][CH:6]=2)[CH2:9][C:10]([OH:12])=[O:11])=[CH:16][N:17]=[CH:18]1

참가 물질

7

반응물 4

HCID 3939Lithium HydroxideHCID 10796Cesium carbonateHCID 27355976-(Bromomethyl)-1,1,4,4-Tetramethyl-1,2,3,4-TetrahydronaphthaleneHCID 57835788(S)-ethyl 3-(4-hydroxyphenyl)-3-(1-methyl-1H-imidazol-5-yl)propanoate

생성물 1

HCID 24967390(S)-3-(1-methyl-1H-imidazol-5-yl)-3-(4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl)propanoic acid수율 53.3%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A mixture of 4.5 (0.15 mmol), 6-(bromomethyl)-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene (0.18 mmol) and cesium carbonate (0.2 mmol) in DMF (2 mL), was stirred at room temperature for 16 hours. To the reaction mixture was added LiOH in water (1 mL, 1N solution), and the reaction was stirred at 50° C. for 3 hours. The mixture was filtered and purified by reverse phase HPLC to give 4 (35 mg, 0.08 mmol) after lyophilization. MS ESI (pos.) m/e 447.3 (M+H). 1H NMR (500 MHz) (CDCl3) δ 8.64 (1 H, s), 7.59 (1 H, s), 7.33-7.36 (2 H, m), 7.20 (1 H, dd, J=7.9, 1.8 Hz), 7.08 (2 H, d, J=8.5 Hz), 6.98 (2 H, d, J=8.5 Hz), 4.98 (2 H, s), 4.53 (1 H, m), 3.57 (3 H, s), 2.96-3.06 (2 H, m), 1.71 (4 H, s), 1.31 (6 H, s), 1.30 (6 H, s).

후처리

  1. stirringthe reaction was stirred at 50° C. for 3 hours
  2. filtrationThe mixture was filtered
  3. custompurified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-d542af5be5474e359ff2ff5331b09a73
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07687526B2

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