Acetic Acid → 7-(2-{1-[2-(4-Cyanophenoxy)ethyl]-3,3-dimethylureido}ethyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester

HRID 899151Notes

Reaction equation

HRID 899151 reaction equation
[C:1]([C:3]1[CH:20]=[CH:19][C:6]([O:7][CH2:8][CH2:9][N:10]([CH2:16][CH:17]=O)[C:11]([N:13]([CH3:15])[CH3:14])=[O:12])=[CH:5][CH:4]=1)#[N:2].[C:21]([O:25][C:26]([N:28]1[CH2:35][CH:34]2[O:36][CH:30]([CH2:31][NH:32][CH2:33]2)[CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(O)(=O)C.[BH3-]C#N.[Na+]>ClCCl.O>[C:21]([O:25][C:26]([N:28]1[CH2:29][CH:30]2[O:36][CH:34]([CH2:33][N:32]([CH2:17][CH2:16][N:10]([CH2:9][CH2:8][O:7][C:6]3[CH:19]=[CH:20][C:3]([C:1]#[N:2])=[CH:4][CH:5]=3)[C:11]([N:13]([CH3:15])[CH3:14])=[O:12])[CH2:31]2)[CH2:35]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 185404123-Boc-9-oxa-3,7-diazabicyclo[3.3.1]nonaneHCID 860865631-[2-(4-Cyanophenoxy)ethyl]-3,3-dimethyl-1-(2-oxoethyl)urea

Product 1

HCID 690786487-(2-{1-[2-(4-Cyanophenoxy)ethyl]-3,3-dimethylureido}ethyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl esterYield 102.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

1-[2-(4-Cyanophenoxy)ethyl]-3,3-dimethyl-1-(2-oxoethyl)urea (4.5 g; see Preparation G above) was taken in dichloromethane (100 mL). 9-Oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester (2.9 g, 0.013 mol; see WO 01/28992), followed by glacial acetic acid (1.47 g, 0.0245 mol), was added, and reaction mixture was stirred for 1 h. NaBH3CN (1.54 g, 0.024 mol) was added at 0° C., and stirring was continued overnight at room temperature. The reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was washed with water and brine and then dried over sodium sulfate. Solvent evaporation, followed by purification by column chromatography, yielded the title compound (6.5 g).

Workup

  1. additionwas added
  2. customreaction mixture
  3. stirringstirring
  4. waitwas continued overnight at room temperature
  5. extractionextracted with dichloromethane
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. customSolvent evaporation
  9. customfollowed by purification by column chromatography

Sources & evidence

ORD record
ord-4c082f8c0ba5468e85ea4840b3555b6c
Source dataset
uspto-grants-2008_04
Patent number
US07354917B2

Reaction notes

Loading…