9H-Fluoren-9-ylmethyl ((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),4,14(18),15-tetraen-12-yl)carbamate → (9S,12R)-12-Amino-9-isopropyl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-11-one

HRID 1022993Notes

Reaction equation

HRID 1022993 reaction equation
C1C2C(COC(=O)[NH:17][C@@H:18]3[CH2:33][C:32]4=[CH:34][CH:35]=[C:29]([CH:30]=[CH:31]4)[O:28][CH2:27][CH:26]=[CH:25][CH2:24][O:23][CH2:22][C@H:21]([CH:36]([CH3:38])[CH3:37])[NH:20][C:19]3=[O:39])C3C(=CC=CC=3)C=2C=CC=1>CO.[Pd]>[NH2:17][C@@H:18]1[CH2:33][C:32]2=[CH:31][CH:30]=[C:29]([CH:35]=[CH:34]2)[O:28][CH2:27][CH2:26][CH2:25][CH2:24][O:23][CH2:22][C@H:21]([CH:36]([CH3:37])[CH3:38])[NH:20][C:19]1=[O:39]

Participants

4

Reactant 1

HCID 683028049H-Fluoren-9-ylmethyl ((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),4,14(18),15-tetraen-12-yl)carbamate

Product 1

HCID 58360483(9S,12R)-12-Amino-9-isopropyl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-11-oneYield 71.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of 6.82 g (12.62 mmol) of 9H-fluoren-9-ylmethyl((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),4,14(18),15-tetraen-12-yl)-carbamate and 4.4 g of 10% Pd/C in 880 ml of methanol was stirred under a hydrogen atmosphere at RT. After 6 h, it was filtered and freed of solvent. The residue was separated by preparative HPLC. The required fractions were combined, acetonitrile was evaporated off, and the resulting aqueous solution was made slightly alkaline with sodium bicarbonate. The aqueous phase was extracted several times with ethyl acetate, and the combined organic phases were dried over sodium sulfate, filtered and concentrated. Chromatography on silica gel with ethyl acetate/methanol mixtures afforded the title compound (2.90 g).

Workup

  1. filtrationit was filtered
  2. customThe residue was separated by preparative HPLC
  3. customacetonitrile was evaporated off
  4. extractionThe aqueous phase was extracted several times with ethyl acetate
  5. dry with materialthe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-6842dbf5ebbb40a4b2cccc33584cf7ed
Source dataset
uspto-grants-2014_05
Patent number
US08722655B2

Reaction notes

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