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

HRID 1369945Notes

Reaction equation

HRID 1369945 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+].N.C(Cl)[Cl:41]>C(O)C>[OH2:15].[ClH:41].[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

7

Reactant 5

HCID 222AmmoniaHCID 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. Ammonia, 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. customto give a thick suspension
  4. stirring5.3 g diatomaceous earth and the mixture was stirred
  5. filtrationfiltered through diatomaceous earth
  6. washThe filtrate was washed 2 times with brine
  7. customthen dried
  8. customchromatographed
  9. washeluting with methylene chloride/methanol/concentrated ammonia 90:10:1
  10. dissolutiondissolved in methylene chloride/isopropyl ether
  11. customHydrogen chloride gas was bubbled in
  12. customProduct was evaporate to dryness

Sources & evidence

ORD record
ord-949839f884ba47278fa0b5cc2dedde62
Source dataset
uspto-grants-2003_06
Patent number
US06579871B2

Reaction notes

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