Sodium hydride → 4-((2-Tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-6-chloro-2-methylpyrimidine

HRID 2175423Notes

Reaction equation

HRID 2175423 reaction equation
[C:1]([O:5][CH:6]1[CH:8]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][N:10]=2)[CH:7]1[CH2:16][OH:17])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Cl:20][C:21]1[CH:26]=[C:25](Cl)[N:24]=[C:23]([CH3:28])[N:22]=1>C1COCC1>[C:1]([O:5][CH:6]1[CH:8]([C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][N:10]=2)[CH:7]1[CH2:16][O:17][C:25]1[CH:26]=[C:21]([Cl:20])[N:22]=[C:23]([CH3:28])[N:24]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2349974,6-Dichloro-2-methylpyrimidineHCID 71271332(2-Tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methanol

Product 1

HCID 867295764-((2-Tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-6-chloro-2-methylpyrimidineYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (2-tert-butoxy-3-(5-methylpyridin-2-yl)cyclopropyl)-methanol (12-5) (130 mg, 0.55 mmol) in THF, sodium hydride (28 mg, 0.69 mmol) was added at 0° C. and it was allowed to stir for 30 min whereupon a solution of 4,6-dichloro-2-methylpyrimidine (113 mg, 0.69 mmol) in THF was added. The solution was heated to reflux overnight. After cooling, it was quenched with water, extracted with EtOAc, dried over sodium sulfate, concentrated under reduced pressure and purified by Pre-TLC (PE/EA=1:1) to afford the product as a white solid (111 mg, 56%). 1H NMR (500 MHz, CDCl3) δ 8.35 (s, 1H), 7.41 (d, J=6.6 Hz, 1H), 7.04 (d, J=8.1 Hz, 1H), 6.59 (s, 1H), 4.49-4.40 (m, 2H), 3.62 (dd, J=6.9, 3.6 Hz, 1H), 2.60 (s, 3H), 2.30 (s, 3H), 2.27 (m, 1H), 2.04 (dd, J=6.7, 3.7 Hz, 1H), 1.08 (s, 9H); LRMS (ES) calculated M+H for C19H25ClN3O2: 362.8. Found: 362.1.

Workup

  1. additionwas added
  2. temperatureThe solution was heated
  3. temperatureto reflux overnight
  4. temperatureAfter cooling
  5. customit was quenched with water
  6. extractionextracted with EtOAc
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. custompurified by Pre-TLC (PE/EA=1:1)

Sources & evidence

ORD record
ord-d7599e6788af4b8198ccacbe2aeddd6e
Source dataset
uspto-grants-2015_06
Patent number
US09062059B2

Reaction notes

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