Lithium hydroxide, monohydrate → (R)-6-Chloro-1'-[2-(1-hydroxy-ethyl)-pyrimidin-4-yl]-spiro[chroman-2,4'-piperidin]-4-one

HRID 394515Notes

Reaction equation

HRID 394515 reaction equation
C([O:6][C@@H:7]([C:9]1[N:14]=[C:13]([N:15]2[CH2:20][CH2:19][C:18]3([CH2:29][C:28](=[O:30])[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([Cl:31])[CH:26]=4)[O:21]3)[CH2:17][CH2:16]2)[CH:12]=[CH:11][N:10]=1)[CH3:8])(=O)CCC.O.[OH-].[Li+]>O1CCCC1.CO.O>[Cl:31][C:25]1[CH:26]=[C:27]2[C:22](=[CH:23][CH:24]=1)[O:21][C:18]1([CH2:19][CH2:20][N:15]([C:13]3[CH:12]=[CH:11][N:10]=[C:9]([C@H:7]([OH:6])[CH3:8])[N:14]=3)[CH2:16][CH2:17]1)[CH2:29][C:28]2=[O:30]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 54550021(R)-1'-[2-(1-Butyryloxy-ethyl)-pyrimidin-4-yl]-6-chloro-spiro[chroman-2,4'-piperidin]-4-one

Product 1

HCID 20825277(R)-6-Chloro-1'-[2-(1-hydroxy-ethyl)-pyrimidin-4-yl]-spiro[chroman-2,4'-piperidin]-4-oneYield 18%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A mixture of (R)-1′-[2-(1-butyryloxy-ethyl)-pyrimidin-4-yl]-6-chloro-spiro[chroman-2,4′-piperidin]-4-one (prepared according to the method of Example 78, Step B, 270 mg, 0.61 mmol) and lithium hydroxide hydrate (80 mg, 1.83 mmol) in a 3:1:1 mixture of tetrahydrofuran/methanol/water (5 mL) was stirred at room temperature for 1.5 h. The organic solvents were evaporated and the residue was extracted with chloroform (4×). The combined organic extracts were dried over sodium sulfate, filtered, evaporated, and purified by flash column chromatography (ethyl acetate) to give 41 mg (18%) of the title compound as a reddish foam. 1H NMR (CDCl3, 300 MHz) δ 8.19 (d, 1H), 7.82 (d, 1H), 7.44 (dd, 1H), 6.96 (d, 1H), 6.40 (d, 1H), 4.65 (q, 1H), 4.20 (app s, 2H), 3.42-3.32 (c, 2H), 2.73 (s, 2H), 2.14 (d, 2H), 1.67 (td, 2H), 1.48 (d, 3H); MS (APCI) 374, 376 (MH+); [α]D+12.6 (c 0.5, MeOH).

Workup

  1. customprepared
  2. customThe organic solvents were evaporated
  3. extractionthe residue was extracted with chloroform (4×)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by flash column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-a928211716e6477f9b0d373df8e59075
Source dataset
uspto-grants-2003_08
Patent number
US06602875B2

Reaction notes

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