Benzyl Alcohol → Ethyl 2-(benzyloxycarbonylamino)-1-(tert-butyldimethylsilyloxy)cyclopropanecarboxylate

HRID 38129Notes

Reaction equation

HRID 38129 reaction equation
[Si:1]([O:8][C:9]1([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][CH:10]1C(O)=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CC[N:22]([CH:26](C)C)C(C)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:36])=CC=1.[CH2:46]([OH:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:18]([O:17][C:15]([C:9]1([O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3])[CH2:11][CH:10]1[NH:22][C:26]([O:53][CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:36])=[O:16])[CH3:19]

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 667282072-(Tert-butyldimethylsilyloxy)-2-(ethoxycarbonyl)cyclopropanecarboxylic acid

Product 1

HCID 66728242Ethyl 2-(benzyloxycarbonylamino)-1-(tert-butyldimethylsilyloxy)cyclopropanecarboxylateYield 32%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2-(tert-butyldimethylsilyloxy)-2-(ethoxycarbonyl)cyclopropanecarboxylic acid (4b, 0.335 g, 1.16 mmol) in toluene (5 mL) under nitrogen was treated with Hünig's base (0.260 mL, 1.51 mmol) and the mixture was cooled to 0° C. After this time, DPPA (0.324 mL, 1.51 mmol) was added and the mixture was heated at 90° C. for 30 min, followed by the addition of benzyl alcohol (0.155 mL, 1.51 mmol). After 15 h, the mixture was cooled, diluted with ethyl acetate (75 mL), and washed sequentially with 10% citric acid (2×50 mL), water (50 mL), and saturated NaHCO3 (50 mL). The organic phase was dried (MgSO4), filtered, and concentrated. The residue was purified by silica gel chromatography eluting with 10% EtOAc/hexanes to 100% EtOAc to afford the title compound as a clear oil (0.146 g, 30%): 1H NMR (300 MHz, CDCl3) δ 7.34-7.30 (m, 5H), 5.40-5.38 (m, 1H), 5.21-5.00 (m, 2H), 4.29-4.18 (m, 2H), 4.16-4.09 (m, 1H), 1.50-1.47 (m, 2H), 1.30 (t, J=7.2 Hz, 3H), 0.88 (s, 9H), 0.26-0.07 (m, 6H); Multimode (APCI+ESI) MS m/z 295 [M+H]+.

Workup

  1. temperaturethe mixture was heated at 90° C. for 30 min
  2. temperaturethe mixture was cooled
  3. washwashed sequentially with 10% citric acid (2×50 mL), water (50 mL), and saturated NaHCO3 (50 mL)
  4. dry with materialThe organic phase was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 10% EtOAc/hexanes to 100% EtOAc

Sources & evidence

ORD record
ord-72763b5d273044c182c7dcd0ff9f94f6
Source dataset
uspto-grants-2013_09
Patent number
US08524689B2

Reaction notes

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