Ethanol → HCID 53307211, compound

HRID 1446140Notes

Reaction equation

HRID 1446140 reaction equation
C(O)C.[CH:4]1([NH:7][CH2:8][C@@H:9]2[C@H:13]([F:14])[CH2:12][NH:11][CH2:10]2)[CH2:6][CH2:5]1.[ClH:15].CO.C(OCC)(=O)C>O>[ClH:15].[ClH:15].[CH:4]1([NH:7][CH2:8][C@@H:9]2[C@H:13]([F:14])[CH2:12][NH:11][CH2:10]2)[CH2:6][CH2:5]1

Participants

6

Reactant 4

HCID 702Ethanol2×HCID 8857Ethyl Acetate2×HCID 11147857N-(((3R,4S)-4-Fluoropyrrolidin-3-yl)methyl)cyclopropanamineHCID 21893726Hydrochloride methanol

Product 1

HCID 53307211HCID 53307211, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

360 mL of ethanol was added to 110 g of (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine (equivalent to 758 mmol) to dissolve the compound. While this solution was stirred, 1.38 L of a 10% hydrogen chloride-methanol solution was added dropwise at an internal temperature of 27 to 33° C. 1.68 L of ethyl acetate was then added dropwise for crystallization (internal temperature of 19° C.). The mixture was stirred for 10 minutes at an internal temperature of 19° C. Subsequently, 1.08 L of ethyl acetate was added dropwise at an internal temperature of 18 to 19° C. and the mixture was stirred for 30 minutes at an internal temperature of 18 to 19° C. The resulting crystals were collected by filtration and washed with 600 mL of a 2:1 mixture of ethyl acetate/methanol. The washed product was drained for 30 minutes and dried by air-blowing at 60° C. for 17 hours to give 82.7 g of a crude product as reddish white powder crystals. To the crude product (82.5 g), 0.83 L of ethanol was added and 50 mL of purified water was added dropwise at an external temperature of 60 to 70° C. to dissolve the product (internal temperature of 65° C.). The solution was allowed to cool under stirring and then cooled in a water bath while kept stirred for crystallization (internal temperature of 28.0° C.). The mixture was continuously cooled in a water bath under stirring until its internal temperature was 20° C., after which it was cooled in an ice bath under stirring for 1 hour. The crystallized product was collected by filtration at an internal temperature of 3° C. and washed with 0.25 L of ethanol. The washed product was drained for 30 minutes and air-dried to give 48.2 g of the title compound as brown powder crystals (27% yield in the 2 steps).

Workup

  1. dissolutionto dissolve the compound
  2. stirringThe mixture was stirred for 10 minutes at an internal temperature of 19° C
  3. stirringthe mixture was stirred for 30 minutes at an internal temperature of 18 to 19° C
  4. filtrationThe resulting crystals were collected by filtration
  5. washwashed with 600 mL of a 2:1 mixture of ethyl acetate/methanol
  6. customdried by air-blowing at 60° C. for 17 hours
  7. customto give 82.7 g of a crude product as reddish white powder crystals
  8. dissolutionto dissolve the product (internal temperature of 65° C.)
  9. temperatureto cool
  10. stirringunder stirring
  11. temperaturecooled in a water bath
  12. stirringwhile kept stirred for crystallization (internal temperature of 28.0° C.)
  13. temperatureThe mixture was continuously cooled in a water bath
  14. stirringunder stirring until its internal temperature
  15. customwas 20° C.
  16. temperatureafter which it was cooled in an ice bath
  17. stirringunder stirring for 1 hour
  18. filtrationThe crystallized product was collected by filtration at an internal temperature of 3° C.
  19. washwashed with 0.25 L of ethanol
  20. waitThe washed product was drained for 30 minutes
  21. customair-dried

Sources & evidence

ORD record
ord-c2889064318948188a59413612a88703
Source dataset
uspto-grants-2010_02
Patent number
US07667049B2

Reaction notes

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