Triethylamine → Ammonium hydroxide methanol

HRID 270560Notes

Reaction equation

HRID 270560 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][CH:31]1[C:36](=O)[CH2:35][CH2:34][O:33][CH2:32]1.C([N:40](CC)CC)C.[C:45](O[BH-](OC(=O)C)OC(=O)C)(=[O:47])C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH4+:2].[OH-:12].[NH4+:40].[OH-:33].[CH3:45][OH:47].[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:36]2[CH2:35][CH2:34][O:33][CH2:32][CH:31]2[CH3:30])[CH2:4]1)([CH3:10])[CH3:9]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 141709263-Methyloxan-4-oneHCID 68930927HCID 68930927, compound

Product 3

HCID 14923Ammonium HydroxideHCID 21894508Ammonium hydroxide methanolYield 1%HCID 68597077HCID 68597077, compound

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-methyltetrahydro-4H-pyran-4-one (39 mg, 0.34 mmol), and triethylamine (0.048 mL, 0.34 mmol) in methylene chloride (5 mL) was added sodium triacetoxyborohydride (73 mg, 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 the desired product as an oil. MS calculated for C27H39F3N2O3: (M+H) 497; found 497.2.

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-16e8affef9cc44f090a7f58699380b36
Source dataset
uspto-grants-2008_11
Patent number
US07449467B2

Reaction notes

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