Sodium hydride → HCID 59507518, compound

HRID 1043818Notes

Reaction equation

HRID 1043818 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].[O:17]1[CH2:22][CH2:21][N:20]([C:23]2[N:28]=[C:27](Cl)[CH:26]=[C:25]([Cl:30])[N:24]=2)[CH2:19][CH2:18]1>O1CCCC1>[Cl:30][C:25]1[N:24]=[C:23]([N:20]2[CH2:21][CH2:22][O:17][CH2:18][CH2:19]2)[N:28]=[C:27]([O:14][CH:11]2[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]2)[CH:26]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 27720684-(4,6-Dichloropyrimidin-2-yl)morpholine

Product 1

HCID 59507518HCID 59507518, compoundYield 77.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of N-Boc-4-hydroxy piperidine (2.58 g, 12.81 mmol) in tetrahydrofuran at 0° C. under argon, was added sodium hydride (60%, 512 mg, 12.81 mmol). After stirring for 20 minutes, a solution of 2-morpholino-4,6-dichloropyrimidine (2.0 g, 8.54 mmol) in tetrahydrofuran (20 mL) was added through a syringe. The solution was stirred for 14 hours as the ice bath warmed to room temperature. At this time, the reaction mixture was quenched with water (2 mL), and was partitioned between EtOAc (350 mL) and Na2CO3(sat.) (75 mL). The organic layer was separated, washed with brine (50 mL), dried over Na2SO4, filtered, concentrated and the residue was purified by SiO2 chromatography (15-20% EtOAc in hexanes) to yield tert-butyl 4-(6-chloro-2-morpholinopyrimidin-4-yloxy)piperidine-1-carboxylate as a white solid (2.64 g, 77%). LCMS (m/z): 399.1 (MH+). 1H NMR (CDCl3): δ 6.00 (s, 1H), 5.18 (m, 1H), 3.74 (s, 8H), 3.64-3.74 (m, 2H), 3.28-3.38 (m, 2H), 1.86-1.96 (m, 2H), 1.68-1.78 (m, 2H), 1.44 (s, 9H).

Workup

  1. customAt this time, the reaction mixture was quenched with water (2 mL)
  2. customwas partitioned between EtOAc (350 mL) and Na2CO3(sat.) (75 mL)
  3. customThe organic layer was separated
  4. washwashed with brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified by SiO2 chromatography (15-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5316a279747d4fc28a79dd39f665fbbb
Source dataset
uspto-grants-2013_10
Patent number
US08563549B2

Reaction notes

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