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

HRID 544822Notes

Reaction equation

HRID 544822 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 2 (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 heated to reflux for 3.5 hours, treated with 2-trimethylsilyl-ethanol (13.5 mL, 94.2 mmol), and heated to reflux overnight. The reaction mixture was filtered, diluted with diethyl ether, washed sequentially with 10% aqueous citric acid solution, water, saturated aqueous NaHCO3, water (2×), and 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 dichloromethane, 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 (br m, 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 heated
  2. temperatureto reflux for 3.5 hours
  3. temperatureheated
  4. temperatureto reflux overnight
  5. filtrationThe reaction mixture was filtered
  6. additiondiluted with diethyl ether
  7. washwashed sequentially with 10% aqueous citric acid solution, water, saturated aqueous NaHCO3, water (2×), and brine (2×)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. filtrationfiltered

Sources & evidence

ORD record
ord-d2df0d12186b471195c2fd8df180f65f
Source dataset
uspto-grants-2011_05
Patent number
US07935670B2

Reaction notes

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