Lithium hydroxide, monohydrate → 1-[4-(4-Quinoxalin-2-yl-piperazin-1-yl)-pyrimidin-2-yl]-ethanol

HRID 394504Notes

Reaction equation

HRID 394504 reaction equation
C([O:4][C@@H:5]([C:7]1[N:12]=[C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:28]=[N:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)[CH2:15][CH2:14]2)[CH:10]=[CH:9][N:8]=1)[CH3:6])(=O)C.O.[OH-].[Li+]>O1CCCC1.O.CO>[N:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:27]=[CH:28][C:19]=1[N:16]1[CH2:15][CH2:14][N:13]([C:11]2[CH:10]=[CH:9][N:8]=[C:7]([C@H:5]([OH:4])[CH3:6])[N:12]=2)[CH2:18][CH2:17]1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 10894166(R)-1-[4-(4-Quinoxalin-2-yl-piperazin-1-yl)-pyrimidin-2-yl]-ethyl acetate

Product 1

HCID 110350751-[4-(4-Quinoxalin-2-yl-piperazin-1-yl)-pyrimidin-2-yl]-ethanolYield 90%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of (R)-1-[4-(4-quinoxalin-2-yl-piperazin-1-yl)-pyrimidin-2-yl]-ethyl acetate (prepared according to the method of Example 1, Step A, 14.1 g, 37.2 mmol) in a 3:1:1 mixture of tetrahydrofuran/water/methanol (375 mL) was added lithium hydroxide hydrate (4.7 g, 112 mmol). This mixture was stirred at room temperature for 1 h 45 min, concentrated, and extracted with chloroform (6×). The combined organic extracts were dried over sodium sulfate, filtered, evaporated, and purified by flash column chromatography (2×; 2% methanol/chloroform) to give 11.3 g (90%) of the title compound as a pale yellow solid after tritration with hexanes. mp: 106.5-108° C.; 1H NMR (CDCl3, 250 MHz) δ 8.62 (s, 1H), 8.26 (d, 1H), 7.92 (dd, 1H), 7.72 (dd, 1H), 7.61 (td, 1H), 7.44 (td, 1H), 6.45 (d, 1H), 4.75 (m, 1H), 3.95-3.85 (c, 8H), 1.54 (d, 3H); MS (Cl/NH3) 337 (MH+); [α]D+15.3 (c 2.3, MeOH).

Workup

  1. concentrationconcentrated
  2. extractionextracted with chloroform (6×)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. custompurified by flash column chromatography (2×; 2% methanol/chloroform)

Sources & evidence

ORD record
ord-7728a9f16a6e49f18cd3e3c5fed830a1
Source dataset
uspto-grants-2003_08
Patent number
US06602875B2

Reaction notes

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