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

HRID 477132ノート

反応式

HRID 477132 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0c78bed6ccb44289840fa15bcb56797d
出典データセット
uspto-grants-1989_12
特許番号
US04886814

反応ノート

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