Benzyl succinimido carbonate → HCID 86705287, compound

HRID 879231Notes

Reaction equation

HRID 879231 reaction equation
C(OC([NH:11][C:12]1[CH:13]=[N:14][CH:15]=[CH:16][C:17]=1[C@@H:18]1[CH2:27][C@H:26]([CH3:28])[C:21]2([O:25][CH2:24][CH2:23][O:22]2)[C@H:20]([NH:29][C:30](=[O:39])[O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:19]1)=O)C1C=CC=CC=1.C(ON1C(=O)CCC1=O)(OCC1C=CC=CC=1)=O>CO.C(Cl)Cl.CCOC(C)=O.[Pd]>[NH2:11][C:12]1[CH:13]=[N:14][CH:15]=[CH:16][C:17]=1[C@H:18]1[CH2:27][C@@H:26]([CH3:28])[C:21]2([O:22][CH2:23][CH2:24][O:25]2)[C@@H:20]([NH:29][C:30](=[O:39])[O:31][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:19]1.[NH2:11][C:12]1[CH:13]=[N:14][CH:15]=[CH:16][C:17]=1[C@@H:18]1[CH2:27][C@H:26]([CH3:28])[C:21]2([O:22][CH2:23][CH2:24][O:25]2)[C@H:20]([NH:29][C:30](=[O:39])[O:31][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:19]1

Participants

8

Reactant 2

HCID 83172Benzyl succinimido carbonateHCID 86705285HCID 86705285, compound

Product 2

HCID 86705287HCID 86705287, compoundYield 28%HCID 86705288HCID 86705288, compoundYield 13%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(+/−)-Benzyl ((6R,8R,10S)-8-(3-((benzoxycarbonyl)amino)pyridin-4-yl)-10-methyl-1,4-dioxaspiro[4.5]decan-6-yl)carbamate (1.0 equiv.) was dissolved in MeOH (0.10 M) and degassed with Argon to vacuum. Pd/C (0.05 equiv.) was added and the mixture was stirred under a H2 balloon for 20 hrs. The mixture was filtered and concentrated. The crude and CBZ-OSu (0.99 equiv.) were dissolved in DCM (0.20 M). The reaction was stirred at room temperature for 2 hrs. The solution was diluted with EtOAc and washed with water, dried over sodium sulfate, filtered and concentrated. The crude residue was purified by ISCO chromatography. Purification was completed via SFC (40% EtOH, 15 mL/min, OJ column) to yield benzyl (6S,8S,10R)-8-(3-aminopyridin-4-yl)-10-methyl-1,4-dioxaspiro[4.5]decan-6-ylcarbamate (28% yield, 99% ee) and benzyl (6R,8R,10S)-8-(3-aminopyridin-4-yl)-10-methyl-1,4-dioxaspiro[4.5]decan-6-ylcarbamate (13% yield, 99% ee). LC/MS (m/z)=398.2 (MH+), Rt=0.64 min.

Workup

  1. customdegassed with Argon to vacuum
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated
  4. stirringThe reaction was stirred at room temperature for 2 hrs
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by ISCO chromatography
  10. customPurification

Sources & evidence

ORD record
ord-eceac986632d41a7bb343726575e297b
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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