Formic Acid → 8-((1R)-2-Chloro-1-hydroxyethyl)-6-(phenylmethoxy)-2H-1,4-benzoxazin-3(4H)-one

HRID 1662957ノート

反応式

HRID 1662957 の反応式
C(O)=O.C(N(CC)CC)C.[CH2:11]([O:18][C:19]1[CH:20]=[C:21]([C:30](=[O:33])[CH2:31][Cl:32])[C:22]2[O:27][CH2:26][C:25](=[O:28])[NH:24][C:23]=2[CH:29]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CN(C)C=O>[CH2:11]([O:18][C:19]1[CH:20]=[C:21]([C@@H:30]([OH:33])[CH2:31][Cl:32])[C:22]2[O:27][CH2:26][C:25](=[O:28])[NH:24][C:23]=2[CH:29]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

参加物

5

反応物 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 211001328-(2-Chloroacetyl)-6-(phenylmethoxy)-2H-1,4-benzoxazin-3(4H)-one

生成物 1

HCID 211001338-((1R)-2-Chloro-1-hydroxyethyl)-6-(phenylmethoxy)-2H-1,4-benzoxazin-3(4H)-one

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

The method is carried out analogously to a process described in the literature (Org. Lett. 2002, 4, 4373-4376). 8 mL of a mixture of formic acid and triethylamine (molar ratio=5:2) are added dropwise at −15° C. to 13.15 g (39.6 mmol) 6-benzyloxy-8-(2-chloro-acetyl)-4H-benzo[1,4]oxazin-3-one and 25.5 mg (0.04 mmol) Cp*RhCl[(S,S)-TsDPEN] (Cp*=pentamethylcyclopentadienyl and TsDPEN=(1S,2S)—N-p-toluenesulfonyl-1,2-diphenylethylenediamine) in 40 mL dimethylformamide. The mixture is stirred for 5 hours at this temperature, then 25 mg catalyst are added and the mixture is stirred overnight at −15° C. The reaction mixture is combined with ice water and filtered. The filter residue is dissolved in dichloromethane, dried with sodium sulfate and freed from the solvent. The residue is chromatographed (dichloromethane/methanol gradient) and the product recrystallized from diethyl ether/diisopropylether. Yield: 10.08 g (76%); Rf value=0.28 (dichloromethane:methanol=50:1 on silica gel).

後処理

  1. stirringthe mixture is stirred overnight at −15° C
  2. filtrationfiltered
  3. dissolutionThe filter residue is dissolved in dichloromethane
  4. dry with materialdried with sodium sulfate
  5. customThe residue is chromatographed (dichloromethane/methanol gradient)
  6. customthe product recrystallized from diethyl ether/diisopropylether

出典と根拠

ORDレコード
ord-3b99877b6c374208a081848deafa55c3
出典データセット
uspto-grants-2011_10
特許番号
US08034809B2

反応ノート

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