1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl ester

HRID 643253

Reaction equation

HRID 643253 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].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>[C:1]([O:5][C:6](=[O:7])[NH: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)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1037871,3,3-Trimethyl-6-azabicyclo(3.2.1)octaneHCID 27559314-{[(Tert-butoxy)carbonyl]amino}benzoic acid

Product 1

HCID 9907515[4-(1,3,3-Trimethyl-6-aza-bicyclo[3.2.1]octane-6-carbonyl)-phenyl]carbamic acid tert-butyl esterYield 77.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 4-tert-butoxycarbonylamino-benzoic acid (50 g, 0.21 mol) and HOBT (31,33 g, 0.231 mol) in dry THF (0.5 L) was added EDAC (44.44 g, 0.231 mol). The resulting mixture was stirred for 10 min followed by addition of a mixture of DIPEA (40.4 ml, 0.231 mol) and 1,3,3-trimethyl-6-aza-bicyclo[3.2.1]octane (39.4 ml, 0.231 mol). The reaction mixture was stirred for an additional 16 hrs. and evaporated to dryness. To the residue was added water (600 ml) and the resulting mixture was extracted with EtOAc (3×500 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 (1:2) as eluent. Pure fractions were collected and evaporated to dryness. To the solid residue was added diethyl ether (100 ml) and the precipitate was filtered off, washed with diethyl ether and dried in vacuo at 50° C. affording 60.5 g (77%) of the title compound as a solid.

Workup

  1. stirringThe reaction mixture was stirred for an additional 16 hrs
  2. customand evaporated to dryness
  3. additionTo the residue was added water (600 ml)
  4. extractionthe resulting mixture was extracted with EtOAc (3×500 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 (1:2) as eluent
  10. customPure fractions were collected
  11. customevaporated to dryness
  12. additionTo the solid residue was added diethyl ether (100 ml)
  13. filtrationthe precipitate was filtered off
  14. washwashed with diethyl ether
  15. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-3dc2c513dab6426cb7d0a78dcddf652d
Source dataset
uspto-grants-2010_04
Patent number
US07700583B2

Linked notes

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