Hydrochloric Acid → N-[2-(4-Carbomethoxymethoxyphenyl)-1-methylethyl]-2-hydroxy-2-(2-trifluoromethyl-thiazol-4-yl)ethanamine

HRID 1451442Notes

Reaction equation

HRID 1451442 reaction equation
[OH:1][CH:2]([C:5]1[N:6]=[C:7]([C:10]([F:13])([F:12])[F:11])[S:8][CH:9]=1)[CH2:3][NH2:4].[C:14]([CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27](=O)[CH3:28])=[CH:22][CH:21]=1)([O:16][CH3:17])=[O:15].C([BH3-])#N.[Na+].Cl>CO>[C:14]([CH2:18][O:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:26][CH:27]([NH:4][CH2:3][CH:2]([OH:1])[C:5]2[N:6]=[C:7]([C:10]([F:13])([F:12])[F:11])[S:8][CH:9]=2)[CH3:28])=[CH:24][CH:25]=1)([O:16][CH3:17])=[O:15]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5003444Sodium cyanoborohydrideHCID 13851156Methyl 2-(4-(2-oxopropyl)phenoxy)acetateHCID 140762394-Thiazolemethanol, alpha-(aminomethyl)-2-(trifluoromethyl)-

Product 1

HCID 14347763N-[2-(4-Carbomethoxymethoxyphenyl)-1-methylethyl]-2-hydroxy-2-(2-trifluoromethyl-thiazol-4-yl)ethanamineYield 92%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Prepared by analogy to Example 13 by reaction of 2-hydroxy-2-(2-trifluoromethyl-thiazol-4-yl)ethanamine with 1-(4-carbomethoxymethoxyphenyl)propan-2-one and sodium cyanoborohydride in methanol (reaction time: 5 hours) followed by purification on a silica gel column using methylene chloride/methanol=20:1. This results in a 50:50 diastereomer mixture of the base. This is recrystallised from a mixture of ether/ethyl acetate=65:10. The mother liquor resulting from this is mixed with ethereal hydrochloric acid, and the mixture is evaporated to dryness. The residue resulting from this is recrystallised from a mixture of ether/ethyl acetate/methanol=100:60:1. The mother liquor obtained after the crystals have been removed by filtration is evaporated to dryness, and the base is liberated by shaking with alkali and methylene chloride and purified on a silica gel column using methylene chloride/methanol=20:1 as eluant. This results in diastereomer B as an oil approximately 92-94% pure.

Workup

  1. customfollowed by purification on a silica gel column
  2. customThis results in a 50:50 diastereomer mixture of the base
  3. customThis is recrystallised from a mixture of ether/ethyl acetate=65:10
  4. customThe mother liquor resulting from
  5. customthe mixture is evaporated to dryness
  6. customThe residue resulting from
  7. customthis is recrystallised from a mixture of ether/ethyl acetate/methanol=100:60:1
  8. customThe mother liquor obtained after the crystals
  9. customhave been removed by filtration
  10. customis evaporated to dryness
  11. custompurified on a silica gel column

Sources & evidence

ORD record
ord-d4e5c6e15f0947709154177879d0e4c1
Source dataset
uspto-grants-1997_02
Patent number
US05604225

Reaction notes

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