Diisobutylaluminum hydride → 2-Cyclopropyl-2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-ethanol

HRID 528474Notes

Reaction equation

HRID 528474 reaction equation
C[O:2][C:3](=O)[CH:4]([CH:20]1[CH2:22][CH2:21]1)[O:5][C:6]1[C:7]([Cl:19])=[N:8][C:9]([Cl:18])=[N:10][C:11]=1[N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.CC(C[AlH]CC(C)C)C>C1COCC1>[CH:20]1([CH:4]([O:5][C:6]2[C:7]([Cl:19])=[N:8][C:9]([Cl:18])=[N:10][C:11]=2[N:12]2[CH2:13][CH2:14][O:15][CH2:16][CH2:17]2)[CH2:3][OH:2])[CH2:22][CH2:21]1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 86711756Cyclopropyl-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-acetic acid methyl ester

Product 1

HCID 867117572-Cyclopropyl-2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of cyclopropyl-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-acetic acid methyl ester (233 mg, 0.64 mmol) in THF (6.5 mL) at −78° C. under an atmosphere of nitrogen was added DIBAL-H (1.93 mL, 1.93 mmol, 1.0M in toluene) dropwise. The reaction mixture was warmed to RT and stirred for 20 hours before being quenched with Rochelle's salt (15 mL, 1M aqueous solution). The mixture was extracted with ethyl acetate (3×30 mL) and the combined organic phases were dried (Na2SO4) then concentrated in vacuo to give 2-Cyclopropyl-2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-ethanol as a colorless gum (215 mg, quantitative). 1H NMR (CDCl3): δ 3.94-3.88 (2H, m), 3.87-3.82 (4H, m), 3.79-3.73 (4H, m), 3.48-3.41 (1H, m), 1.11-0.99 (1H, m), 0.60-0.51 (1H, m), 0.51-0.42 (1H, m), 0.19-0.11 (1H, m), 0.03-−0.05 (1H, m).

Workup

  1. custombefore being quenched with Rochelle's salt (15 mL, 1M aqueous solution)
  2. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
  3. dry with materialthe combined organic phases were dried (Na2SO4)
  4. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-eb1b949e58244623a933c0a9eadc1b49
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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