Oxalyl chloride → 2-{[(2R)-1,4-dioxan-2-ylmethyl]sulfanyl}-2-methyl-N-{3-[(3S)-2-methyl-3-(oxan-2-yloxy)butan-2-yl]-1,2-oxazol-5-yl}propanamide

HRID 386917ノート

反応式

HRID 386917 の反応式
[O:1]1[CH2:6][CH2:5][O:4][CH2:3][C@@H:2]1[CH2:7][S:8][C:9]([CH3:14])([CH3:13])[C:10]([OH:12])=O.C(Cl)(=O)C(Cl)=O.[CH3:21][C:22]([C:33]1[CH:37]=[C:36]([NH2:38])[O:35][N:34]=1)([C@@H:24]([O:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][O:28]1)[CH3:25])[CH3:23].C(N(CC)C(C)C)(C)C>CN(C=O)C.C(Cl)Cl.C1COCC1>[O:1]1[CH2:6][CH2:5][O:4][CH2:3][C@@H:2]1[CH2:7][S:8][C:9]([CH3:14])([CH3:13])[C:10]([NH:38][C:36]1[O:35][N:34]=[C:33]([C:22]([CH3:21])([C@@H:24]([O:26][CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][O:28]2)[CH3:25])[CH3:23])[CH:37]=1)=[O:12]

参加物

8

反応物 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 592532413-[(3S)-2-methyl-3-(oxan-2-yloxy)butan-2-yl]-1,2-oxazol-5-amineHCID 592532592-{[(2R)-1,4-dioxan-2-ylmethyl]sulfanyl}-2-methylpropanoic acid

生成物 1

HCID 592531802-{[(2R)-1,4-dioxan-2-ylmethyl]sulfanyl}-2-methyl-N-{3-[(3S)-2-methyl-3-(oxan-2-yloxy)butan-2-yl]-1,2-oxazol-5-yl}propanamide収率 85.3%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

Activation of 145 mg (0.58 mmol) of 2-{[(2R)-1,4-dioxan-2-ylmethyl]sulfanyl}-2-methylpropanoic acid as its acid chloride is achieved by treatment with oxalyl chloride (0.1 mL, 1.16 mmol) and DMF (1 drop) in DCM (15 mL) at room temperature for 16 h. The solvent is removed under reduced pressure and the crude acid chloride is dissolved in anhydrous THF (5 mL) and added to a solution of 147 mg (0.58 mmol) of 3-[(3S)-2-methyl-3-(oxan-2-yloxy)butan-2-yl]-1,2-oxazol-5-amine and N,N-diisopropylethylamine (0.30 mL, 1.73 mmol) in THF (10 mL). The reaction is heated to 60° C. for 18 h. After cooling to room temperature, the reaction mixture is concentrated under reduced pressure. The residue is diluted with DCM (20 mL) and washed with saturated aqueous NaHCO3 solution (10 mL). The organic layer is dried (MgSO4), filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography (silica, eluent: heptanes, 0-30% ethyl acetate) to afford 226 mg of 2-{[(2R)-1,4-dioxan-2-ylmethyl]sulfanyl}-2-methyl-N-{3-[(3S)-2-methyl-3-(oxan-2-yloxy)butan-2-yl]-1,2-oxazol-5-yl}propanamide of 63% purity. This intermediate is taken on in the next step without further purification. Yield: 54%, ES-MS: m/z 479 [M+Na]

後処理

  1. customThe solvent is removed under reduced pressure
  2. dissolutionthe crude acid chloride is dissolved in anhydrous THF (5 mL)
  3. temperatureAfter cooling to room temperature
  4. concentrationthe reaction mixture is concentrated under reduced pressure
  5. additionThe residue is diluted with DCM (20 mL)
  6. washwashed with saturated aqueous NaHCO3 solution (10 mL)
  7. dry with materialThe organic layer is dried (MgSO4)
  8. filtrationfiltered
  9. concentrationthe filtrate is concentrated under reduced pressure
  10. customThe residue is purified by column chromatography (silica, eluent: heptanes, 0-30% ethyl acetate)

出典と根拠

ORDレコード
ord-bf46f7c04d624facb0529c771669e615
出典データセット
uspto-grants-2013_02
特許番号
US08372874B2

反応ノート

読み込み中…