Acetic Acid → 2-[(3R*,4S*)-1-{[2-Chloro-6-(trifluoromethyl)phenyl]methyl}-3-{[1-(cyclohex-1-en-1-ylmethyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetic acid

HRID 446009Notes

Reaction equation

HRID 446009 reaction equation
[C:1]1([CH:7]=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:36])[F:35])[C:29]=1[CH2:38][N:39]1[CH2:43][C@@H:42]([CH3:44])[C@@:41]([CH2:54][C:55]([OH:57])=[O:56])([C:45](=[O:53])[NH:46][CH:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)[CH2:40]1>O1CCCC1.CO.O>[Cl:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:35])([F:37])[F:36])[C:29]=1[CH2:38][N:39]1[CH2:43][C@@H:42]([CH3:44])[C@@:41]([CH2:54][C:55]([OH:57])=[O:56])([C:45](=[O:53])[NH:46][CH:47]2[CH2:48][CH2:49][N:50]([CH2:7][C:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=3)[CH2:51][CH2:52]2)[CH2:40]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 51845401-Cyclohexene-1-carboxaldehydeHCID 712937542-[(3R*,4S*)-1-{[2-Chloro-6-(trifluoromethyl)phenyl]methyl}-4-methyl-3-[(piperidin-4-yl)carbamoyl]pyrrolidin-3-yl]acetic acid

Product 1

HCID 712936432-[(3R*,4S*)-1-{[2-Chloro-6-(trifluoromethyl)phenyl]methyl}-3-{[1-(cyclohex-1-en-1-ylmethyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetic acidYield 43.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Cyclohex-1-ene-1-carbaldehyde (423 μl, 3.73 mmol), acetic acid (300 μl) and sodium triacetoxyborohydride (789 mg, 3.73 mmol) were added to a solution of the mixture of 2-[(3R*,4S*)-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-4-methyl-3-[(piperidin-4-yl)carbamoyl]pyrrolidin-3-yl]acetic acid obtained by the method of Example 3d (344 mg, 0.745 mmol) in tetrahydrofuran (dehydrated) (10 mL), followed by stirring overnight. Water and methanol were added to the reaction liquid, which was concentrated under reduced pressure, and the residue was purified by ODS column chromatography (elution solvent: water/methanol). The purified product was dissolved in dichloromethane, suspended by adding hexane and concentrated to give the title compound (180 mg, yield: 43.4%).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. customthe residue was purified by ODS column chromatography (elution solvent: water/methanol)
  3. dissolutionThe purified product was dissolved in dichloromethane
  4. additionby adding hexane
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-01b9347ea5ac4695b289dfc4debff7d7
Source dataset
uspto-grants-2013_07
Patent number
US08476301B2

Reaction notes

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