Sodium hydride → HCID 67540255, compound

HRID 1192386Notes

Reaction equation

HRID 1192386 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl[C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[CH:20][N:19]=1>CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 788644-ChloroquinazolineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 67540255HCID 67540255, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred suspension of NaH (60%, 0.146 g, 3.65 mmol) in DMF (15 mL) was added dropwise a solution of 4-Hydroxypiperidine-1-carboxylic acid tert-butyl ester (0.611 g, 3.04 mmol) in DMF (5 mL) at 0° C. The reaction was stirred for 1 hour and then 4-chloroquinazoline (0.500 g, 3.04 mmol) was added. The mixture was allowed to warm to room temperature and stirred overnight. The mixture was partitioned between H2O and EtOAc. The aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by column chromatography (hexanes:EtOAc, 2:1) to give 4-(Quinazolin-4-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (0.76 g, 76%) as a colorless oil. Removal of the Boc group by the procedures described in Example 34, Step 3 afforded 4-(Piperidin-4-yloxy)-quinazoline dihydrochloride as a white solid. 1H NMR (CD3OD, 400 MHz) δ 9.35 (s, 1H), 8.59 (d, J=8.4 Hz, 1H), 8.31 (td, J=7.2 Hz, J=1.2 Hz 1H), 8.11 (d, J=8.4 Hz, 1H), 8.04 (t, J=7.2 Hz, 1H), 6.00 (m, 1H), 3.55 (m, 2H), 3.40 (m, 2H), 2.42 (m, 4H). LCMS (APCI+) m/z 230 [M+H]+; Rt=1.67 min.

Workup

  1. stirringstirred overnight
  2. customThe mixture was partitioned between H2O and EtOAc
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (hexanes:EtOAc, 2:1)

Sources & evidence

ORD record
ord-6b66b932c2a34e1ea7bd59990774ec8d
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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