N-Hydroxyphthalimide → 7-[3,5-Dihydroxy-2-(3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-5-heptenoic acid 1,3-dioxo-1,3-dihydro-isoindol-2-yl ester

HRID 591123Notes

Reaction equation

HRID 591123 reaction equation
CCN[C:4]([CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][C@@H:12]1[C@@H:16](/[CH:17]=[CH:18]/[C@@H:19]([OH:28])[CH2:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@H:15]([OH:29])[CH2:14][C@@H:13]1[OH:30])=[O:5].[OH:31][N:32]1[C:36](=[O:37])[C:35]2=[CH:38][CH:39]=[CH:40][CH:41]=[C:34]2[C:33]1=[O:42].C(N=C=NC(C)C)(C)C.OS([O-])(=O)=O.[Na+]>C1COCC1.COC(C)(C)C>[O:37]=[C:36]1[C:35]2[C:34](=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:33](=[O:42])[N:32]1[O:31][C:4](=[O:5])[CH2:6][CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH:12]1[CH:13]([OH:30])[CH2:14][CH:15]([OH:29])[CH:16]1[CH:17]=[CH:18][CH:19]([OH:28])[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 10665N-HydroxyphthalimideHCID 12734DiisopropylcarbodiimideHCID 516919Sodium BisulfateHCID 5311027Bimatoprost

Product 1

HCID 867188447-[3,5-Dihydroxy-2-(3-hydroxy-5-phenyl-pent-1-enyl)-cyclopentyl]-5-heptenoic acid 1,3-dioxo-1,3-dihydro-isoindol-2-yl esterYield 58.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

2 g of bimatoprost acid is dissolved in 20 ml of THF and to this solution are added at room temperature 1 g of N-hydroxy-phtalimide and 1 ml of N,N′-diisopropylcarbodiimide. The reaction mixture is stirred for 2 hours and then poured onto they mixture of 1N NaHSO4 solution and tert-butyl methyl ether (TBME). The phases are separated, the organic phase is washed with 1N NaHCO3 solution and the aqueous-alkaline phase is extracted with TBME. The united organic phase is dried over Na2SO4, filtered and evaporated. The residue is crystallized from hexane:acetone mixture to obtain 1.5 g white crystalline material.

Workup

  1. customThe phases are separated
  2. washthe organic phase is washed with 1N NaHCO3 solution
  3. extractionthe aqueous-alkaline phase is extracted with TBME
  4. dry with materialThe united organic phase is dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is crystallized from hexane

Sources & evidence

ORD record
ord-ad00af67107b4dd7aad85ac24db0a68e
Source dataset
uspto-grants-2016_01
Patent number
US09238621B2

Reaction notes

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