Morpholine → HCID 66955430, compound

HRID 2386658Notes

Reaction equation

HRID 2386658 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1>CN1CCCC1=O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]1[CH2:10][CH2:11][CH:12]([C:15]([N:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[O:17])[CH2:13][CH2:14]1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27559964-(((Tert-butoxy)carbonyl)amino)cyclohexane-1-carboxylic acid

Product 1

HCID 66955430HCID 66955430, compoundYield 46.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 4-tert-butoxycarbonylamino-cyclohexanecarboxylic acid (10.0 g, 41 mmol), EDCI (23.64 g, 123 mmol) and HOBt (18.88 g, 123 mmol) in 1-methyl-2-pyrrolidinone (150 mL) was stirred at RT for 3 hours. Morpholine (10.75 mL, 123 mmol) was then added, and the resulting mixture was stirred at RT for 78 hours. The reaction was quenched by adding water and the resulting mixture was extracted with EtOAc. The organic layer was separated and washed twice with K2CO3 (sat'd aq) and an HCl (aq, 10%), again with once with a saturated K2CO3 (sat'd aq) and with brine. The organic layer was then dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The crude residue was triturated with Et2O and filtered to give 5.9 g of [4-(morpholine-4-carbonyl)-cyclohexyl]-carbamic acid tert-butyl ester as a white powder.

Workup

  1. stirringthe resulting mixture was stirred at RT for 78 hours
  2. customThe reaction was quenched
  3. additionby adding water
  4. extractionthe resulting mixture was extracted with EtOAc
  5. customThe organic layer was separated
  6. washwashed twice with K2CO3 (sat'd aq)
  7. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customThe crude residue was triturated with Et2O
  11. filtrationfiltered

Sources & evidence

ORD record
ord-8fa79bcecfed412e94880e080467f72c
Source dataset
uspto-grants-2012_09
Patent number
US08268840B2

Reaction notes

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