Diazomethane → (1R,2S)-ethyl 1-(tert-butoxycarbonylamino)-2-cyclopropylcyclopropanecarboxylate

HRID 270667Notes

Reaction equation

HRID 270667 reaction equation
[C:1]([NH:8][C@:9]1([C:14]([OH:16])=[O:15])[CH2:11][C@H:10]1[CH:12]=[CH2:13])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[N+](=C)=[N-].[CH3:20][CH2:21]OC(C)=O.[CH3:26]CCCCC>CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:20]([O:15][C:14]([C@@:9]1([NH:8][C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:11][C@H:10]1[CH:12]1[CH2:26][CH2:13]1)=[O:16])[CH3:21]

Participants

6

Reactant 3

HCID 9550DiazomethaneHCID 10376443(1R,2S)-1-(((1,1-Dimethylethoxy)carbonyl)amino)-2-ethenylcyclopropanecarboxylic acidHCID 21226206Ethyl acetate hexane

Product 1

HCID 59990838(1R,2S)-ethyl 1-(tert-butoxycarbonylamino)-2-cyclopropylcyclopropanecarboxylateYield 78%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

A solution of N-Boc-(1R,2S)-1-amino-2-vinylcyclopropane carboxylic acid (255 mg, 1.0 mmol) in ether (10 mL) was treated with palladium acetate (5 mg, 0.022 mmol). The orange/red solution was placed under an atmosphere of N2. An excess of diazomethane in ether was added dropwise over the course of 1 h. The resulting solution was stirred at rt for 18 h. The excess diazomethane was removed using a stream of nitrogen. The resulting solution was concentrated by rotary evaporation to give the crude product. Flash chromatography (10% EtOAc/hexane) provided 210 mg (78%) of N-Boc-(1R,2S)-1-amino-2-cyclopropylcyclopropane carboxylic acid ethyl ester as a colorless oil. LC-MS (retention time: 2.13, similar to method A except: gradient time 3 min, Xterra MS C18 S7 3.0×50 mm column), MS m/e 270 (M++1).

Workup

  1. customThe excess diazomethane was removed
  2. concentrationThe resulting solution was concentrated by rotary evaporation
  3. customto give the crude product

Sources & evidence

ORD record
ord-42be7577958b42959942187c91785ea2
Source dataset
uspto-grants-2008_11
Patent number
US07449479B2

Reaction notes

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