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

HRID 1662957노트

반응식

HRID 1662957 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-3b99877b6c374208a081848deafa55c3
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08034809B2

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