2-(Piperidin-4-yl)-1,3-benzothiazole → alpha-(R)-(3-(S)-((4-(benzothiazol-2-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid, 4-methoxybenzyl ester

HRID 1068143Notes

Reaction equation

HRID 1068143 reaction equation
[CH:1]([C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][N:5]([C@H:14]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[O:16])[CH2:4]1)=O.[NH:33]1[CH2:38][CH2:37][CH:36]([C:39]2[S:40][C:41]3[CH:47]=[CH:46][CH:45]=[CH:44][C:42]=3[N:43]=2)[CH2:35][CH2:34]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[S:40]1[C:41]2[CH:47]=[CH:46][CH:45]=[CH:44][C:42]=2[N:43]=[C:39]1[CH:36]1[CH2:35][CH2:34][N:33]([CH2:1][C@@H:3]2[C@@H:7]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:6][N:5]([C@H:14]([CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)[C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:16])[CH2:4]2)[CH2:38][CH2:37]1

Participants

5

Reactant 3

HCID 14774392-(Piperidin-4-yl)-1,3-benzothiazoleHCID 5049666Sodium triacetoxyborohydrideHCID 53654320alpha-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester

Product 1

HCID 57100094alpha-(R)-(3-(S)-((4-(benzothiazol-2-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid, 4-methoxybenzyl esterYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 52 mg of α-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid, 4-methoxybenzyl ester (prepared above as Aldehyde 5) and 50 mg of 2-(piperidin-4-yl)benzothiazole (from Step B) in 2.5 mL of THF was added two spatula tips of 3 Å molecular sieves. After stirring at room temperature for 20 mim., 50 mg of sodium triacetoxyborohydride was added and the reaction was stirred at room temperature for 18 hours. The reaction was quenched with MeOH and diluted with EtOAc. After filtering molecular sieves, the filtrate was concentrated under reduced pressure. The residue was partitioned between EtOAc and water. The organic layer was washed with brine and dried over anhydrous MgSO4. Concentration under reduced pressure followed by flash chromatography eluting with 20% EtOAc in hexane followed by 50% EtOAc in hexane afforded 56 mg of the title compound as a white solid.

Workup

  1. stirringthe reaction was stirred at room temperature for 18 hours
  2. customThe reaction was quenched with MeOH
  3. additiondiluted with EtOAc
  4. filtrationAfter filtering molecular sieves
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was partitioned between EtOAc and water
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous MgSO4
  9. concentrationConcentration under reduced pressure
  10. washeluting with 20% EtOAc in hexane

Sources & evidence

ORD record
ord-9fc759afbf49490398c06cdb171b41b9
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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