Dicyclohexylcarbodiimide → HCID 22952776, compound

HRID 276765Notes

Reaction equation

HRID 276765 reaction equation
[C:1]([N:8]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[F:17][C:18]1[C:23](O)=[C:22]([F:25])[C:21]([F:26])=[C:20]([F:27])[C:19]=1[F:28].C1(N=C=NC2CCCCC2)CCCCC1>C(OCC)(=O)C>[F:17][C:18]1[C:23]([O:11][C:10](=[O:12])[C@@H:9]2[CH2:13][C@@H:14]([OH:16])[CH2:15][N:8]2[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])=[C:22]([F:25])[C:21]([F:26])=[C:20]([F:27])[C:19]=1[F:28]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 13041PentafluorophenolHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 22952776HCID 22952776, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

Boc-trans-4-hydroxy-L-proline (3.5 kg) (prepared as described in Step 1) and pentafluorophenol (3.06 kg) were dissolved in ethyl acetate (52 L). The solution was treated with a solution of dicyclohexylcarbodiimide (3.43 kg) in ethyl acetate (8 L) and the mixture was stirred at room temperature for 2 hours. The resulting slurry was cooled to 0° C., filtered and the solids washed with ethyl acetate (15 L). The filtrate was evaporated at atmospheric pressure to a volume of 10 L and diluted with hexane (100 L). The resulting mixture was stirred at room temperature overnight and then cooled to 0° C. for 1 hour. The solid was collected by filtration, washed with cold (° C.) 10:1 hexane/ethyl acetate (15 L) and dried at 45° C. in vacuo to afford the title compound as a white crystalline solid.

Workup

  1. temperatureThe resulting slurry was cooled to 0° C.
  2. filtrationfiltered
  3. washthe solids washed with ethyl acetate (15 L)
  4. customThe filtrate was evaporated at atmospheric pressure to a volume of 10 L
  5. additiondiluted with hexane (100 L)
  6. stirringThe resulting mixture was stirred at room temperature overnight
  7. temperaturecooled to 0° C. for 1 hour
  8. filtrationThe solid was collected by filtration
  9. washwashed with cold (° C.) 10:1 hexane/ethyl acetate (15 L)
  10. customdried at 45° C. in vacuo

Sources & evidence

ORD record
ord-f1db21529bbb42b0b20d7bb1c7a2a8d4
Source dataset
uspto-grants-2002_03
Patent number
US06355611B1

Reaction notes

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