Triethylamine → 3-Ethoxy-N-[(1R,3S)-3-isopropyl-3-({4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)cyclopentyl]tetrahydro-2H-pyran-4-amine

HRID 1044558Notes

Reaction equation

HRID 1044558 reaction equation
Cl.Cl.[CH:3]([C@:6]1([C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=3)[CH2:16][CH2:15]2)=[O:13])[CH2:10][CH2:9][C@@H:8]([NH2:11])[CH2:7]1)([CH3:5])[CH3:4].[CH2:30]([O:32][CH:33]1[C:38](=O)[CH2:37][CH2:36][O:35][CH2:34]1)[CH3:31].C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CCOC(C)=O>[CH2:30]([O:32][CH:33]1[CH:38]([NH:11][C@@H:8]2[CH2:9][CH2:10][C@:6]([CH:3]([CH3:5])[CH3:4])([C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:28])([F:29])[F:27])[CH:21]=4)[CH2:16][CH2:15]3)=[O:13])[CH2:7]2)[CH2:37][CH2:36][O:35][CH2:34]1)[CH3:31]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 235335993-Ethoxyoxan-4-oneHCID 68932997(1R,3S)-3-isopropyl-3-({4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)cyclopentanamine dihydrochloride

Product 1

HCID 579387113-Ethoxy-N-[(1R,3S)-3-isopropyl-3-({4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)cyclopentyl]tetrahydro-2H-pyran-4-amineYield 102.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1R,3S)-3-isopropyl-3-({4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}carbonyl)cyclopentanamine dihydrochloride (200 mg, 0.438 mmol), 3-ethoxytetrahydro-4H-pyran-4-one (130 mg, 0.88 mmol) and triethylamine (0.18 mL, 1.3 mmol) in methylene chloride (10 mL) was added sodium triacetoxyborohydride (180 mg, 0.88 mmol). After being stirred at room temperature overnight, the reaction mixture was diluted with EtOAc and washed with saturated Na2CO3. The aqueous layer was extracted with EtOAc three times. The combined organic layers were dried (MgSO4), concentrated and purified on silica gel (EtOAc to 1% Et3N/EtOAc to 5% Et3N/EtOAc) affording 230 mg of product. The product was separated by chiral HPLC to give two major isomers: isomer 1 (110 mg) and isomer 2 (77 mg). MS calculated for C27H40F3N3O3: (M+H) 512; found 512.2.

Workup

  1. washwashed with saturated Na2CO3
  2. extractionThe aqueous layer was extracted with EtOAc three times
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated
  5. custompurified on silica gel (EtOAc to 1% Et3N/EtOAc to 5% Et3N/EtOAc)

Sources & evidence

ORD record
ord-d1f8eaa8c5594601a2740330e5c87639
Source dataset
uspto-grants-2013_10
Patent number
US08563582B2

Reaction notes

Loading…