Dichloromethane → 2-(3,5-Di-t-butyl-4-hydroxyphenyl)-4-(2-(4-methylethylaminomethylphenoxy) ethyl)-5-methyloxazole hydrochloride hydrate

HRID 1276959Notes

Reaction equation

HRID 1276959 reaction equation
[CH3:1][NH:2][CH2:3][CH3:4].[C:5]([C:9]1[CH:10]=[C:11]([C:20]2[O:21][C:22]([CH3:36])=[C:23]([CH2:25][CH2:26][O:27][C:28]3[CH:33]=[CH:32][C:31]([CH:34]=O)=[CH:30][CH:29]=3)[N:24]=2)[CH:12]=[C:13]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:14]=1[OH:15])([CH3:8])([CH3:7])[CH3:6].[BH4-].[Na+].C(Cl)[Cl:40]>C(O)C>[OH2:15].[ClH:40].[C:16]([C:13]1[CH:12]=[C:11]([C:20]2[O:21][C:22]([CH3:36])=[C:23]([CH2:25][CH2:26][O:27][C:28]3[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][C:33]=3[CH2:1][NH:2][CH2:3][CH3:4])[N:24]=2)[CH:10]=[C:9]([C:5]([CH3:6])([CH3:8])[CH3:7])[C:14]=1[OH:15])([CH3:18])([CH3:19])[CH3:17]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 12219N-MethylethylamineHCID 4311764Sodium borohydrideHCID 1357250662-(3,5-Di-t-butyl-4-hydroxyphenyl)-4-(2-(4-formylphenoxy)ethyl)-5-methyloxazole

Product 1

HCID 1364704832-(3,5-Di-t-butyl-4-hydroxyphenyl)-4-(2-(4-methylethylaminomethylphenoxy) ethyl)-5-methyloxazole hydrochloride hydrateYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methylethylamine, 0.71 ml (8.32 mmole) and 2.46 ml (8.32 mmole) Ti(OPr)4 were dissolved in 17 ml of ethanol and stirred for 10 minutes under nitrogen. Compound of step D, 1.75 g (4.16 mmole), was added and the mixture was stirred for 4 hours. Sodium borohydride, 240 mg (6.23 mmole) was added and the reaction was stirred for 3 days. Asponia, 5.8 ml 2N, was added to give a thick suspension. Methylene chloride (40 ml) was added then 5.3 g diatomaceous earth and the mixture was stirred, and filtered through diatomaceous earth. The filtrate was washed 2 times with brine then dried. The organics were stripped and chromatographed, eluting with methylene chloride/methanol/concentrated ammonia 90:10:1. Fractions were bulked, stripped, dissolved in methylene chloride/isopropyl ether. Hydrogen chloride gas was bubbled in. Product was evaporate to dryness to give 1.36 g (63%) of a white foam.

Workup

  1. stirringthe mixture was stirred for 4 hours
  2. stirringthe reaction was stirred for 3 days
  3. additionAsponia, 5.8 ml 2N, was added
  4. customto give a thick suspension
  5. stirring5.3 g diatomaceous earth and the mixture was stirred
  6. filtrationfiltered through diatomaceous earth
  7. washThe filtrate was washed 2 times with brine
  8. customthen dried
  9. customchromatographed
  10. washeluting with methylene chloride/methanol/concentrated ammonia 90:10:1
  11. dissolutiondissolved in methylene chloride/isopropyl ether
  12. customHydrogen chloride gas was bubbled in
  13. customProduct was evaporate to dryness

Sources & evidence

ORD record
ord-6d85c3d9550b441b847b1cafad866701
Source dataset
uspto-grants-2000_12
Patent number
US06166216

Reaction notes

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