Triethylamine → 1-({(1S,3R)-1-Isopropyl-3-[(3-methoxytetrahydro-2H-pyran-4-yl)amino]cyclopentyl}carbonyl)-4-[2-(trifluoromethyl)phenyl]piperidin-4-ol

HRID 1436776Notes

Reaction equation

HRID 1436776 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:7][CH2:6][C@@:5]([C:11]([N:13]2[CH2:18][CH2:17][C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:28])[F:27])([OH:19])[CH2:15][CH2:14]2)=[O:12])([CH:8]([CH3:10])[CH3:9])[CH2:4]1.[CH3:30][O:31][CH:32]1[C:37](=O)[CH2:36][CH2:35][O:34][CH2:33]1.C([N:41](CC)CC)C.[C:46](O[BH-](OC(=O)C)OC(=O)C)(=[O:48])C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH4+:2].[OH-:12].[NH4+:41].[OH-:31].[CH3:46][OH:48].[CH:8]([C@:5]1([C:11]([N:13]2[CH2:18][CH2:17][C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:29])([F:27])[F:28])([OH:19])[CH2:15][CH2:14]2)=[O:12])[CH2:6][CH2:7][C@@H:3]([NH:2][CH:37]2[CH2:36][CH2:35][O:34][CH2:33][CH:32]2[O:31][CH3:30])[CH2:4]1)([CH3:10])[CH3:9]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 235336103-Methoxyoxan-4-oneHCID 689309271-{[(1S,3R)-3-amino-1-isopropylcyclopentyl]carbonyl}-4-[2-(trifluoromethyl)phenyl]piperidin-4-ol hydrochloride

Product 3

HCID 14923Ammonium HydroxideHCID 116492051-({(1S,3R)-1-Isopropyl-3-[(3-methoxytetrahydro-2H-pyran-4-yl)amino]cyclopentyl}carbonyl)-4-[2-(trifluoromethyl)phenyl]piperidin-4-olYield 58.5%HCID 21894508Ammonium hydroxide methanolYield 1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-{[(1S,3R)-3-amino-1-isopropylcyclopentyl]carbonyl}-4-[2-(trifluoromethyl) phenyl]piperidin-4-ol hydrochloride (50 mg, 0.1 mmol) , 3-methoxytetrahydro-4H-pyran-4-one (45 mg, 0.34 mmol) , and triethylamine (0.048 mL, 0.34 mmol) in methylene chloride (2 mL) was added sodium triacetoxyborohydride (0.073 g, 0.34 mmol). After being stirred overnight at room temperature, a saturated solution of NaHCO3 was added. The solution was extracted with methylene chloride three times. The combined extracts were dried (MgSO4), filtered, and concentrated. Purification by flash chromatography on silica gel (0-20% B over 15 min. Bottle A=1% NH4OH/2% MeOH/EtOAc, Bottle B=1% NH4OH/MeOH) afforded 15 mg of the desired product as an oil. MS calculated for C27H39F3N2O4:(M+H) 513; found 513.2.

Workup

  1. extractionThe solution was extracted with methylene chloride three times
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel (0-20% B over 15 min

Sources & evidence

ORD record
ord-82726dea443749d9bbb60bf79f80a4e8
Source dataset
uspto-grants-2009_11
Patent number
US07618970B2

Reaction notes

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