Carbon Dioxide → HCID 25112455, compound

HRID 1678097Notes

Reaction equation

HRID 1678097 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][C@@H:10]1[CH2:16][CH2:15][CH2:14][CH2:13][NH:12][C:11]1=[O:17].O.ON1C2C=CC=CC=2N=N1.[C:29]([O:33][C:34]([N:36]([CH3:53])[C@H:37]([CH2:44][C:45]1[CH:50]=[CH:49][C:48]([Cl:51])=[C:47]([Cl:52])[CH:46]=1)[C@H:38]([OH:43])[CH2:39][C:40](O)=[O:41])=[O:35])([CH3:32])([CH3:31])[CH3:30].C1(N=C=NC2CCCCC2)CCCCC1.C(=O)([O-])O.[K+].C(=O)=O>CN(C)C=O.O>[C:29]([O:33][C:34](=[O:35])[N:36]([C@H:37]([CH2:44][C:45]1[CH:50]=[CH:49][C:48]([Cl:51])=[C:47]([Cl:52])[CH:46]=1)[C@H:38]([OH:43])[CH2:39][C:40](=[O:41])[NH:9][C@@H:10]1[CH2:16][CH2:15][CH2:14][CH2:13][NH:12][C:11]1=[O:17])[CH3:53])([CH3:32])([CH3:30])[CH3:31]

Participants

10

Reactant 7

HCID 280Carbon DioxideHCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 516893Potassium BicarbonateHCID 27960291-Hydroxybenzotriazole hydrateHCID 51358597(3R)-3-Aminoazepan-2-one--hydrogen chloride (1/1)HCID 67004551HCID 67004551, compound

Product 1

HCID 25112455HCID 25112455, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent4×

Conditions

Temperature
2.5 °C

Procedure

Triethylamine (1.396 g=1.91 ml, 13.8 mmol) is added to a stirred mixture of (R)-3-amino-azepan-2-one hydrochloride (7) in N,N-dimethylformamide (12 ml) at 18-22° C., then stirring is continued for approx. 1 hour. 1-Hydroxybenzotriazole hydrate (2.113 g, 13.8 mmol) is added at 18-22° C. to the stirred mixture, followed by the solution of (3R,4R)-4-tert-butoxycarbonyl-methyl-amino)-5-(3,4-dichloro-phenyl)-3-hydroxy-pentanoic acid (6) in N,N-dimethyl-formamide. N,N-dimethylformamide (2 ml) is used for rinsing. The mixture is cooled to 0-5° C., then 1,3-dicyclohexylcarbodiimide (2.847 g, 13.8 mmol) is added, followed by N,N-dimethylformamide (1.5 ml), used for rinsing. Stirring at approx. 0-5° C. is continued for approx. 1 hour, then the mixture is warmed to approx. 18-22° C. and stirred at that temperature for approx. 20 hours. The precipitated solids are removed by filtration and the filter cake is rinsed with N,N-dimethylformamide (12 ml). The filtrate is concentrated at a mantle temperature of approx. 60° C. under reduced pressure, until a concentrate of approx. 19.5 g is obtained. The resulting suspension is cooled to approx. 20-25° C., then an aqueous solution of potassium hydrogencarbonate (1.92 g, 19.17 mmol) in water (32 ml) is added over a period of approx. 20 minutes under evolution of carbon dioxide to give a suspension. The precipitated solids are isolated by filtration, rinsed with water (24 ml) and dried in vacuo at approx. 60° C. to constant weight to yield crude [(1R,2R)-1-(3,4-dichloro-benzyl)-2-hydroxy-3-((R)-2-oxo-azepan-3-ylcarbamoyl)-propyl]-methyl-carbamic acid tert-butyl ester (8) (6.019 g, 99.8% of theory based on (R)-2-(tert-butoxycarbonyl-methyl-amino)-3-(3,4-dichloro-phenyl-propionic acid (1).

Workup

  1. washfor rinsing
  2. washfor rinsing
  3. stirringStirring at approx. 0-5° C.
  4. waitis continued for approx. 1 hour
  5. temperaturethe mixture is warmed to approx. 18-22° C.
  6. stirringstirred at that temperature for approx. 20 hours
  7. customThe precipitated solids are removed by filtration
  8. washthe filter cake is rinsed with N,N-dimethylformamide (12 ml)
  9. concentrationThe filtrate is concentrated at a mantle temperature of approx. 60° C. under reduced pressure
  10. concentrationuntil a concentrate of approx. 19.5 g
  11. customis obtained
  12. temperatureThe resulting suspension is cooled to approx. 20-25° C.
  13. customto give a suspension
  14. customThe precipitated solids are isolated by filtration
  15. washrinsed with water (24 ml)
  16. customdried in vacuo at approx. 60° C. to constant weight

Sources & evidence

ORD record
ord-880c6c8ccc614c4480f7fd7b00f005f7
Source dataset
uspto-grants-2011_08
Patent number
US08008479B2

Reaction notes

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