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

HRID 1662957Notes

Reaction equation

HRID 1662957 reaction equation
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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-3b99877b6c374208a081848deafa55c3
Source dataset
uspto-grants-2011_10
Patent number
US08034809B2

Reaction notes

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