Acetic Acid → rac-ethyl (1R,2R)-1-amino-2-ethylcyclopropane-1-carboxylate

HRID 1918337Notes

Reaction equation

HRID 1918337 reaction equation
[CH2:1]([O:3][C:4]([C@@:6]1([NH:11]C(OC(C)(C)C)=O)[CH2:8][C@H:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2].[K+].[K+].N(C([O-])=O)=NC([O-])=O.C(O)(=O)C>CO>[CH2:1]([O:3][C:4]([C@@:6]1([NH2:11])[CH2:8][C@H:7]1[CH2:9][CH3:10])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 176Acetic Acid2×HCID 6096233Potassium diazene-1,2-dicarboxylate2×HCID 10658673Ethyl (1R,2S)-1-[[(1,1-dimethylethoxy)carbonyl]amino]-2-ethenylcyclopropanecarboxylate

Product 1

HCID 58218933rac-ethyl (1R,2R)-1-amino-2-ethylcyclopropane-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

(1R,2S)-1-tert-Butoxycarbonylamino-2-vinyl-cyclopropanecarboxylic acid ethyl ester (400 mg, 1.57 mmol) was dissolved in methanol (5 ml) and added to a suspension of azodicarboxylic acid dipotassium salt (1.46 g, 7.5 mmol; cf. D. J. Pasto et al., Organic Reactions 40 (1991), 91-155) in methanol (10 ml). Acetic acid (1.12 g, 18.8 mmol) was added in the course of 10 min and the mixture was stirred for 1 h at room temperature. Azodicarboxylic acid dipotassium salt (1.46 g) and acetic acid (1.12 g) were added once again and the mixture stirred for 1 h. LC/MS analysis then indicated complete conversion. The volatiles were evaporated, the residue was partitioned between EA and a saturated sodium hydrogencarbonate solution, and the combined organic extracts were dried over sodium chloride, decanted over a small plug of silica gel and evaporated to dryness. The obtained intermediate was dissolved in a mixture of DCM (5 ml) and TFA (1 ml) and stirred for 1 h at room temperature. The volatiles were evaporated, and the residue was partitioned between diethyl ether and saturated sodium hydrogencarbonate solution. The combined organic extracts were dried over sodium chloride, decanted and evaporated to dryness to yield the title compound.

Workup

  1. stirringthe mixture stirred for 1 h
  2. customThe volatiles were evaporated
  3. customthe residue was partitioned between EA
  4. dry with materiala saturated sodium hydrogencarbonate solution, and the combined organic extracts were dried over sodium chloride
  5. customdecanted over a small plug of silica gel
  6. customevaporated to dryness
  7. dissolutionThe obtained intermediate was dissolved in a mixture of DCM (5 ml) and TFA (1 ml)
  8. stirringstirred for 1 h at room temperature
  9. customThe volatiles were evaporated
  10. customthe residue was partitioned between diethyl ether and saturated sodium hydrogencarbonate solution
  11. dry with materialThe combined organic extracts were dried over sodium chloride
  12. customdecanted
  13. customevaporated to dryness

Sources & evidence

ORD record
ord-564f0dfc5c9f41889aa29c0274fb03ad
Source dataset
uspto-grants-2013_12
Patent number
US08618304B2

Reaction notes

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