1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (4-Benzyloxy-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanone

HRID 643270Notes

Reaction equation

HRID 643270 reaction equation
[CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.[CH3:48][C:49]12[CH2:56][CH:53]([NH:54][CH2:55]1)[CH2:52][C:51]([CH3:58])([CH3:57])[CH2:50]2>C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]([N:54]2[CH2:55][C:49]3([CH3:48])[CH2:56][CH:53]2[CH2:52][C:51]([CH3:58])([CH3:57])[CH2:50]3)=[O:15])=[CH:16][CH:17]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 738804-(Benzyloxy)benzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1037871,3,3-Trimethyl-6-azabicyclo(3.2.1)octane

Product 1

HCID 11439902(4-Benzyloxy-phenyl)-(1,3,3-trimethyl-6-aza-bicyclo[3.2.1]oct-6-yl)-methanoneYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 4-benzyloxy-benzoic acid (0.5 g, 2.191 mmol) and HOBT (326 mg, 2.41 mmol) in dry THF (50 ml) was added EDAC (462 mg, 2.41 mmol). The resulting mixture was stirred for 10 min. followed by addition of a mixture of DIPEA (420 μl, 2.41 mmol) and 1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane (410 μl, 2.41 mmol). The reaction mixture was stirred for an additional 16 hrs. and evaporated to dryness. To the residue was added water (50 ml) and the resulting mixture was extracted with EtOAc (2×50 ml). The combined organic phases were dried (Na2SO4), filtered and evaporated in vacuo. The resulting residue was purified by column chromatography (silica gel) using a mixture of EtOAc-Heptane (1:3) as eluent. Pure fractions were collected and evaporated to dryness affording 610 mg (77%) of the title compound as an oil.

Workup

  1. stirringThe reaction mixture was stirred for an additional 16 hrs
  2. customand evaporated to dryness
  3. additionTo the residue was added water (50 ml)
  4. extractionthe resulting mixture was extracted with EtOAc (2×50 ml)
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe resulting residue was purified by column chromatography (silica gel)
  9. additiona mixture of EtOAc-Heptane (1:3) as eluent
  10. customPure fractions were collected
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-25bfe43bd1dd47f99fe2ad68b8bbfaa1
Source dataset
uspto-grants-2010_04
Patent number
US07700583B2

Reaction notes

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