Lithium hydroxide, monohydrate → 1-[4-(6-Thiophen-3-yl-3,4-dihydro-1H-isoquinolin-2-yl)-pyrimidin-2-yl]-ethanol

HRID 586191Notes

Reaction equation

HRID 586191 reaction equation
C([O:4][C@@H:5]([C:7]1[N:12]=[C:11]([N:13]2[CH2:22][CH2:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:23]4[CH:27]=[CH:26][S:25][CH:24]=4)[CH:19]=3)[CH2:14]2)[CH:10]=[CH:9][N:8]=1)[CH3:6])(=O)C.O.[OH-].[Li+]>CO.O1CCCC1.O>[S:25]1[CH:26]=[CH:27][C:23]([C:18]2[CH:19]=[C:20]3[C:15](=[CH:16][CH:17]=2)[CH2:14][N:13]([C:11]2[CH:10]=[CH:9][N:8]=[C:7]([CH:5]([OH:4])[CH3:6])[N:12]=2)[CH2:22][CH2:21]3)=[CH:24]1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 20767625(R)-1-[4-(6-Thiophen-3-yl-3,4-dihydro-1H-isoquinoline-2-yl)-pyrimidin-2-yl]-ethyl acetate

Product 1

HCID 223286551-[4-(6-Thiophen-3-yl-3,4-dihydro-1H-isoquinolin-2-yl)-pyrimidin-2-yl]-ethanolYield 72%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of (R)-1-[4-(6-thiophen-3-yl-3,4-dihydro-1H-isoquinolin-2-yl)-pyrimidin-2-yl]-ethyl acetate (prepared according to the method of Example 248, Step C, 253 mg, 0.67 mmol) in a 3:1:1 mixture of methanol/tetrahydrofuran/water (5 mL) was added lithium hydroxide hydrate (84 mg, 2.0 mmol). This mixture was stirred at room temperature for 1 h, concentrated, re-suspended in water, and extracted with chloroform (4×). The combined organic extracts were dried over sodium sulfate, filtered, evaporated, and purified by flash column chromatography (2% methanol/chloroform) to give a yellow solid which was further purified by recrystallization, from ether/methanol to give 163 mg (72%) of the title compound as a white solid. mp: 125.5-127.5° C.; 1H NMR (CDCl3, 360 MHz) δ 8.22 (d, 1H), 7.47-7.35 (c, 5H), 7.22 (d, 1H), 6.42 (d, 1H), 4.78-4.72 (c, 2H), 4.46 (br s, 1H), 3.93-3.84 (c, 2H), 2.99 (t, 2H), 1.54 (d, 3H); MS (APCI) 338 (MH+).

Workup

  1. concentrationconcentrated
  2. extractionextracted with chloroform (4×)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. custompurified by flash column chromatography (2% methanol/chloroform)
  7. customto give a yellow solid which
  8. customwas further purified by recrystallization, from ether/methanol

Sources & evidence

ORD record
ord-40aeca2fbdef4417bbe309b1c67820e6
Source dataset
uspto-grants-2005_08
Patent number
US06936600B2

Reaction notes

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