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

HRID 477132Notes

Reaction equation

HRID 477132 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 obtar,ned 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. customhave been removed by filtration
  9. customis evaporated to dryness
  10. custompurified on a silica gel column

Sources & evidence

ORD record
ord-0c78bed6ccb44289840fa15bcb56797d
Source dataset
uspto-grants-1989_12
Patent number
US04886814

Reaction notes

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