Potassium Carbonate → HCID 86599419, compound

HRID 2108705Notes

Reaction equation

HRID 2108705 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([N:13]1[C@H:18]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:17](=[O:23])[NH:16][C@H:15]([CH:24]2[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:25]2)[C:14]1=[O:33])[C:10]([OH:12])=[O:11].C(=O)([O-])[O-].[K+].[K+].[C:40]([O:43][CH:44](Br)[CH3:45])(=[O:42])[CH3:41]>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([N:13]1[C@H:18]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:17](=[O:23])[NH:16][C@H:15]([CH:24]2[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:25]2)[C:14]1=[O:33])[C:10]([O:12][CH2:45][CH2:44][O:43][C:40](=[O:42])[CH3:41])=[O:11]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 111375051-Bromoethyl acetateHCID 11590614(2R)-(2,4-difluorophenyl)[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]ethanoic Acid

Product 1

HCID 86599419HCID 86599419, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2R)-(2,4-difluorophenyl)[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]ethanoic acid (example 22) (0.130 g) was stirred in anhydrous DMF (1 mL) and anhydrous potassium carbonate (0.020 g, 0.5 eq.) was added. The mixture was stirred at room temperature for 1 hour then cooled to −10° C. (ice-salt bath). The heterogeneous mixture was treated with 1-bromoethyl acetate (0.120 mL, excess) and stirred for 3.5 hours keeping the bath temperature between −10 and −5° C. It was then partitioned between DCM and 1M HCl aq. (20 mL each). The organic phase was separated (hydrophobic frit) and evaporated under reduced pressure to give a purple gum; this was purified by SPE cartridge (5 g, silica eluted with (i) cyclohexane x2, (ii) DCM x2, (iii) diethl ether x2, (iv) ethyl acetate x2, (v) methanol x2 to give I -(acetyloxy)ethyl (2R)-(2,4-difluorophenyl)[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]ethanoate (0.081 g) as a yellow foam.

Workup

  1. stirringstirred for 3.5 hours
  2. customthe bath temperature between −10 and −5° C
  3. customIt was then partitioned between DCM and 1M HCl aq. (20 mL each)
  4. customThe organic phase was separated (hydrophobic frit)
  5. customevaporated under reduced pressure
  6. customto give a purple gum
  7. customthis was purified by SPE cartridge (5 g, silica
  8. washeluted with (i) cyclohexane x2, (ii) DCM x2, (iii) diethl ether x2, (iv) ethyl acetate x2, (v) methanol x2

Sources & evidence

ORD record
ord-e112a7e80e8747aa8ed65817fe64d409
Source dataset
uspto-grants-2009_04
Patent number
US07514437B2

Reaction notes

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