4-Methylmorpholine → (3R)-3-{3-[(2-Amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}-6-cyclohexyl-N-hydroxyhexanamide

HRID 2182947ノート

反応式

HRID 2182947 の反応式
[NH2:1][C:2](=[O:25])[CH2:3][O:4][CH2:5][C:6]1[N:10]=[C:9]([C@H:11]([CH2:16][CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:12][C:13](O)=[O:14])[O:8][N:7]=1.CN1CCOCC1.ClC(OCC(C)C)=O.C[Si](C)(C)[O:43][NH2:44]>O1CCCC1.CO>[NH2:1][C:2](=[O:25])[CH2:3][O:4][CH2:5][C:6]1[N:10]=[C:9]([C@H:11]([CH2:16][CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:12][C:13]([NH:44][OH:43])=[O:14])[O:8][N:7]=1

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 59909790(3R)-3-{3-[(2-amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}6-cyclohexylhexanoic acid

生成物 1

HCID 9947442(3R)-3-{3-[(2-Amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}-6-cyclohexyl-N-hydroxyhexanamide収率 32.6%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of (3R)-3-{3-[(2-amino-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}-6-cyclohexylhexanoic acid (Preparation 91) (178 mg, 0.50 mmol) and N-methylmorpholine (100 μl, 0.91 mmol) in anhydrous tetrahydrofuran (8 ml) was cooled to 0° C., treated with isobutyl chloroformate (70 μl, 0.54 mmol) and stirred under a nitrogen atmosphere for 2.5 hours. O-(Trimethylsilyl)hydroxylamine (200 μl, 1.63 mmol) was added and the mixture was stirred for 18 hours, being allowed to warm to room temperature over this time. The mixture was then treated with methanol and stirred at room temperature for 1 hour. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed with water and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The oil was purified by column chromatography on silica gel eluting with a gradient system of 98:2 (dichloromethane:methanol) gradually changing to 90:10 (dichloromethane:methanol) and then neat methanol to afford the title compound as a colourless oil (60 mg).

後処理

  1. stirringthe mixture was stirred for 18 hours
  2. stirringstirred at room temperature for 1 hour
  3. customThe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe oil was purified by column chromatography on silica gel eluting with a gradient system of 98:2 (dichloromethane:methanol)

出典と根拠

ORDレコード
ord-69d74c85d1534e8ba0765c41e04d204b
出典データセット
uspto-grants-2005_05
特許番号
US06897306B2

反応ノート

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