Triethylamine → (1S,2S) 2-Ethyl-1-(2trimethylsilanylethoxycarbonylamino)cyclopropane-carboxylic acid tert-butyl ester

HRID 1818751Notes

Reaction equation

HRID 1818751 reaction equation
[C:1]([O:5][C:6]([C:8]1(C(O)=O)[CH2:10][CH:9]1[CH2:11][CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:18]([CH2:21]C)CC)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:30])=CC=1.[CH3:40][Si:41]([CH3:46])([CH3:45])[CH2:42][CH2:43][OH:44]>C1C=CC=CC=1>[C:1]([O:5][C:6]([C@:8]1([NH:18][C:21]([O:44][CH2:43][CH2:42][Si:41]([CH3:46])([CH3:45])[CH3:40])=[O:30])[CH2:10][C@@H:9]1[CH2:11][CH3:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 180132-(Trimethylsilyl)ethanolHCID 199401P,P-Diphenylphosphinic azideHCID 666701131-(tert-Butoxycarbonyl)-2-ethylcyclopropane-1-carboxylic acid

Product 1

HCID 86601847(1S,2S) 2-Ethyl-1-(2trimethylsilanylethoxycarbonylamino)cyclopropane-carboxylic acid tert-butyl esterYield 238%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To a suspension of the product of Step 6b (10 g, 46.8 mmol) and 3 g of freshly activated 4 Å molecular sieves in dry benzene (160 mL), was added triethylamine (7.50 mL, 53.8 mmol) and DPPA (11 mL, 10.21 mmol). The reaction mixture was refluxed for 3.5 hours, 2-trimethylsilyl-ethanol (13.5 mL, 94.2 mmol) was then added, and the reaction mixture was refluxed overnight. The reaction mixture was filtered, diluted with diethyl ether, washed with a 10% aqueous citric acid solution, water, saturated aqueous NaHCO3, water (2×), brine (2×), dried (MgSO4), filtered, and concentrated in vacuo. The residue was suspended with 10 g of Aldrich polyisocyanate scavenger resin in 120 mL of CH2Cl2, stirred at room temperature overnight and filtered to provide the desired product (8 g, 24.3 mmol; 52%) as a pale yellow oil: 1H NMR (CDCl3) δ 0.03 (s, 9H), 0.97 (m, 5H), 1.20 (bm, 1H), 1.45 (s, 9H), 1.40-1.70 (m, 4H), 4.16 (m, 2H), 5.30 (br s, 1H).

Workup

  1. temperatureThe reaction mixture was refluxed for 3.5 hours
  2. temperaturethe reaction mixture was refluxed overnight
  3. filtrationThe reaction mixture was filtered
  4. additiondiluted with diethyl ether
  5. washwashed with a 10% aqueous citric acid solution, water, saturated aqueous NaHCO3, water (2×), brine (2×)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. filtrationfiltered

Sources & evidence

ORD record
ord-03adb4fd762049958725d540649d5a92
Source dataset
uspto-grants-2009_10
Patent number
US07601686B2

Reaction notes

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