Ethanol → HCID 86718592, compound

HRID 1480631Notes

Reaction equation

HRID 1480631 reaction equation
[C:1]([N:5]1[CH2:10][C:9]2[CH:11]=[C:12]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:13]=[C:14]([C:15]3[CH:16]=[N:17][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:20]=3)[C:8]=2[O:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[CH:29]1([Mg][Cl:36])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.C(OCC)C.C(O)C>C1COCC1.Cl>[ClH:36].[C:25]([C:12]1[CH:13]=[C:14]([C:15]2[CH:16]=[N:17][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:19][CH:20]=2)[C:8]([OH:7])=[C:9]([CH2:10][N:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:6][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)[CH:11]=1)([CH3:27])([CH3:26])[CH3:28]

Participants

7

Reactant 4

HCID 702EthanolHCID 3283Diethyl EtherHCID 75202150HCID 75202150, compoundHCID 178478990HCID 178478990, compound

Product 1

HCID 86718592HCID 86718592, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3,6-di-tert-butyl-8-(6-(trifluoromethyl)pyridin-3-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine (Example 75) (250 mg, 0.63 mmol) in THF (10 mL) under argon was added dropwise a 2.0 M solution of cyclohexylmagnesium chloride in diethyl ether (0.41 mL, 0.82 mmol). The reaction mixture was stirred at room temperature for 16 hours, and then partitioned between ethyl acetate and a saturated aqueous sodium bicarbonate solution. The organic phase was separated, dried (Na2SO4), filtered, and the crude product purified using flash chromatography on silica eluting with a solvent gradient of 0 to 100% ethyl acetate in hexanes. The product was dissolved in a 1.25 M solution of hydrochloric acid in ethanol (5 mL, 6.3 mmol), the mixture stirred for 30 minutes then concentrated under reduced pressure and the product triturated with hexane to give 4-(tert-butyl)-2-((tert-butyl(cyclohexylmethyl)amino)methyl)-6-(6-(trifluoromethyl)pyridin-3-yl)phenol hydrochloride (162 mg, 50% yield) as a white powder.

Workup

  1. custompartitioned between ethyl acetate
  2. customThe organic phase was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe crude product purified
  6. stirringthe mixture stirred for 30 minutes
  7. concentrationthen concentrated under reduced pressure
  8. customthe product triturated with hexane

Sources & evidence

ORD record
ord-dd30be787fef4aa5b0ccda85afd5db8e
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

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