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

HRID 588546Notes

Reaction equation

HRID 588546 reaction equation
C(OC([C@@]1(N[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])C[C@H]1C1CC1)=O)C.CC[N:22]([CH2:25][CH3:26])[CH2:23]C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:34])=CC=1.[CH3:44][Si:45]([CH3:50])([CH3:49])[CH2:46][CH2:47][OH:48].[CH:51]1[CH:56]=CC=C[CH:52]=1>>[C:16]([O:15][C:13]([C@:25]1([NH:22][C:23]([O:48][CH2:47][CH2:46][Si:45]([CH3:50])([CH3:49])[CH3:44])=[O:34])[CH2:26][C@@H:52]1[CH2:51][CH3:56])=[O:14])([CH3:17])([CH3:18])[CH3:19]

Participants

6

Reactant 5

HCID 241BenzeneHCID 8471TriethylamineHCID 180132-(Trimethylsilyl)ethanolHCID 199401P,P-Diphenylphosphinic azideHCID 59990838(1R,2S)-ethyl 1-(tert-butoxycarbonylamino)-2-cyclopropylcyclopropanecarboxylate

Product 1

HCID 86601847(1S,2S) 2-Ethyl-1-(2trimethylsilanylethoxycarbonylamino)cyclopropane-carboxylic acid tert-butyl esterYield 52%

Procedure

To a suspension, of the product of Step 2 (10 g, 46.8 mmol) and 3 g of freshly activated 4A molecular sieves in dry benzene (160 mL), was added Et3N (7.50 mL, 53.8 mmol) and DPPA (11 mL, 10.21 mmol). The reaction mixture was refluxed for 3.5 h, 2-trimethylsilyl-ethanol (13.5 mL, 94.2 mmol) was then added, and the reaction mixture was refluxed overnite. The reaction mixture was filtered, diluted with Et2O, washed with a 10% aqueous citric acid solution, water, saturated aqueous NaHCO3, water (2×), brine (2×), dried (MgSO4) and concentrated in vacuo. The residue was suspended with 10 g of Aldrich polyisocyanate scavenger resin in 120 mL of CH2Cl2, stirred at rt overnite and filtered to afford the titled 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 (bs, 1H).

Workup

  1. temperatureThe reaction mixture was refluxed for 3.5 h
  2. temperaturethe reaction mixture was refluxed overnite
  3. filtrationThe reaction mixture was filtered
  4. additiondiluted with Et2O
  5. washwashed with a 10% aqueous citric acid solution, water, saturated aqueous NaHCO3, water (2×), brine (2×)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. filtrationfiltered

Sources & evidence

ORD record
ord-45f2965a23064cf4986197653cd4c0b5
Source dataset
uspto-grants-2016_01
Patent number
US09227940B2

Reaction notes

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