Ethyl diazoacetate → HCID 178473104, compound

HRID 1257699Notes

Reaction equation

HRID 1257699 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([OH:14])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[N+](=[CH:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N-]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Rh+3].C([O-])(=O)C.C([O-])(=O)C>[CH2:22]([O:21][C:19](=[O:20])[CH2:18][O:14][C@H:11]1[CH2:10][CH2:9][C@H:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:15])[CH2:13][CH2:12]1)[CH3:23]

Participants

5

Reactant 2

HCID 12192Ethyl diazoacetate2×HCID 178418329HCID 178418329, compound

Product 1

HCID 178473104HCID 178473104, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 168478Rhodium acetateCatalyst2×HCID 1140TolueneSolvent3×

Procedure

A suspension of trans (4-hydroxy-cyclohexyl)-carbamic acid tert-butyl ester (1.03 g, 4.80 mmol) in dry toluene (38 mL) under an nitrogen atmosphere was treated with rhodium acetate (110 mg, 200 μmol) and heated at reflux. A solution of ethyl diazoacetate (600 μL, 5.70 mmol) in dry toluene (9 mL) was added dropwise over 1.5 hours. The mixture was then stirred at reflux for a further 30 minutes and allowed to cool to ambient temperature overnight. The reaction was treated with a further portion of rhodium acetate (50 mg) and re-heated to reflux. Further ethyl diazoacetate (300 μL) in dry toluene (5 mL) was added dropwise over 1 hour. Heating was continued for 30 minutes and then the cooled mixture was concentrated under vacuum. The residue was purified by column chromatography on silica gel (gradient: 0-35% ethyl acetate in cyclohexane) to afford 720 mg (50%) of trans (4-tert-butoxycarbonylamino-cyclohexyloxy)-acetic acid ethyl ester as a white solid. LCMS (Method Q, ESI): RT=3.63 min, m+H=324.0; 1H NMR (400 MHz, CDCl3) δ: 4.35 (br s, 1H), 4.21 (q, 2H), 4.09 (s, 2H), 3.44 (br s, 1H), 3.32 (m, 1H), 2.04 (m, 4H), 1.44 (m, 11H), 1.28 (t, 3H), 1.13 (m, 2H).

Workup

  1. temperatureheated
  2. temperatureat reflux
  3. temperatureat reflux for a further 30 minutes
  4. temperaturere-heated to reflux
  5. temperatureHeating
  6. concentrationthe cooled mixture was concentrated under vacuum
  7. customThe residue was purified by column chromatography on silica gel (gradient: 0-35% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-c2a105703f7541f2bc906e8ff3227443
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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