1-Hydroxybenzotriazole → HCID 178454208, compound

HRID 491878Notes

Reaction equation

HRID 491878 reaction equation
[CH2:1]([O:8][C:9]([C@H:11]1[CH2:16][CH2:15][C@@H:14]([NH:17][CH2:18][CH2:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28]([O:32][C:33]([NH:35][C@H:36]([CH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1)[CH2:37][CH2:38][C:39](O)=[O:40])=[O:34])([CH3:31])([CH3:30])[CH3:29].C1C=CC2N(O)N=NC=2C=1.CNC(N=C=NCC)CCNC>C(Cl)Cl.CCOC(C)=O>[CH2:1]([O:8][C:9]([C@H:11]1[CH2:12][CH2:13][C@@H:14]([N:17]([CH2:18][CH2:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:39](=[O:40])[CH2:38][CH2:37][C@H:36]([NH:35][C:33]([O:32][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:34])[CH:42]2[CH2:43][CH2:44][O:45][CH2:46][CH2:47]2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 230638731,3-Dimethylaminopropyl-3-ethylcarbodiimideHCID 576783374-tert-butoxycarbonylamino-4-(S)-tetrahydro-pyran-4-yl-butyric acidHCID 178525080HCID 178525080, compound

Product 1

HCID 178454208HCID 178454208, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an ice cooled solution of cis-4-(2-benzyloxy-ethylamino)-cyclohexanecarboxylic acid benzyl ester (3 g, 8.2 mmol), 4-tert-butoxycarbonylamino-4-(S)-tetrahydro-pyran-4-yl-butyric acid (2.4 g, 8.4 mmol) (prepared as in Example 35) and HOBT (2.4 g, 10.5 mmol) in CH2Cl2 (100 mL) was added TEA (2.3 mL), followed by addition of 1,3-dimethylamino propyl-3-ethylcarbodiimide (EDC, 2.0 g, 10 mmol). The reaction mixture was allowed to warm to room temperature and then was stirred overnight. EtOAc (200 mL) was added and the resulting mixture washed with citric acid solution, NaHCO3 solution, and aq. NaCl solution. The organic layer was dried with MgSO4. The EtOAc was evaporated to yield a colorless oil. The colorless oil (crude product) was purified by column chromatography (1:1 EtOAc/Hexane) to yield 4-{(2-benzyloxy-ethyl)-[4-tert-butoxycarbonylamino-4-(S)-(tetrahydro-pyran-4-yl)-butyryl]-amino}-cis-cyclohexanecarboxylic acid benzyl ester as a residue.

Workup

  1. washthe resulting mixture washed with citric acid solution, NaHCO3 solution, and aq. NaCl solution
  2. dry with materialThe organic layer was dried with MgSO4
  3. customThe EtOAc was evaporated
  4. customto yield a colorless oil
  5. customThe colorless oil (crude product) was purified by column chromatography (1:1 EtOAc/Hexane)

Sources & evidence

ORD record
ord-21e67cbef7ce46e9870e900935cf2509
Source dataset
uspto-grants-2009_05
Patent number
US07531545B2

Reaction notes

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