Potassium Carbonate → {(3R*,5S*)-5-[Cyclopropyl-(2,3-dimethyl-benzyl)-carbamoyl]-piperidin-3-yl}-carbamic acid tert-butyl ester

HRID 1698327Notes

Reaction equation

HRID 1698327 reaction equation
C1C2C(COC([N:18]3[CH2:23][C@H:22]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][C@H:20]([C:32]([OH:34])=O)[CH2:19]3)=O)C3C(=CC=CC=3)C=2C=CC=1.[CH:35]1([NH:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([CH3:46])[C:41]=2[CH3:47])[CH2:37][CH2:36]1.C(N(C(C)C)C(C)C)C.CCCP(=O)=O.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl.N1CCCCC1>CC(N(C)C)=O.C(OCC)(=O)C>[C:28]([O:27][C:25](=[O:26])[NH:24][C@@H:22]1[CH2:21][C@H:20]([C:32](=[O:34])[N:38]([CH:35]2[CH2:37][CH2:36]2)[CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([CH3:46])[C:41]=2[CH3:47])[CH2:19][NH:18][CH2:23]1)([CH3:29])([CH3:30])[CH3:31]

Participants

9

Reactant 6

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 16167369Propylphosphoric anhydrideHCID 43090146N-(2,3-Dimethylbenzyl)cyclopropanamineHCID 57870323HCID 57870323, compoundHCID 67144590Dichloromethane piperidine

Product 1

HCID 15984736{(3R*,5S*)-5-[Cyclopropyl-(2,3-dimethyl-benzyl)-carbamoyl]-piperidin-3-yl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

To a stirred, ice-cooled mixture of (3S*,5R*)-5-tert-butoxycarbonylamino-piperidine-1,3-dicarboxylic acid 1-(9H-fluoren-9-ylmethyl) ester (5.0 g, 10.7 mmol), cyclopropyl-(2,3-dimethyl-benzyl)-amine (CAS 625437-38-9) (4.41 g, 11.8 mmol) and N-ethyldiisopropylamine (14.7 ml, 85.7 mmol) in dimethylacetamide (50 ml), propylphosphonic anhydride solution (˜50% in DMF, 10 ml, ˜16 mmol) is added. After stirring for 14 h at RT, the residue is distributed between ethyl acetate and 10% aqueous K2CO3 solution. The organic layer is dried (Na2SO4) and evaporated in vacuo. Part of the residue (365 mg, 0.58 mmol) is treated with a mixture of CH2Cl2/piperidine (4:1; 10 ml) and stirred at RT for 1 h. The reaction mixture is then evaporated and the residue purified via preparative HPLC to afford the title compound. MS: 402.5 [M+H]+; tR (HPLC, Nucleodur 100; 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 10 min, flow 1.5 ml/min): 4.77 min.

Workup

  1. temperatureTo a stirred, ice-cooled
  2. additionis added
  3. dry with materialThe organic layer is dried (Na2SO4)
  4. customevaporated in vacuo
  5. stirringstirred at RT for 1 h
  6. customThe reaction mixture is then evaporated
  7. customthe residue purified via preparative HPLC

Sources & evidence

ORD record
ord-9aba40981eda4bd89ca299cd13eda075
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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