Acetic Acid → Cyclopentyl-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetra-hydropyran-4-ylmethyl}amine

HRID 272882

Reaction equation

HRID 272882 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][NH2:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(=O)C.C(N(CC)CC)C.[C:35]1(=O)[CH2:39][CH2:38][CH2:37][CH2:36]1>ClC(Cl)C>[CH:35]1([NH:23][CH2:22][C:16]2([C:13]3[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:11][CH:12]=3)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)[CH2:39][CH2:38][CH2:37][CH2:36]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8452CyclopentanoneHCID 8471TriethylamineHCID 11645410(4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine

Product 1

HCID 23091703Cyclopentyl-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetra-hydropyran-4-ylmethyl}amineYield 73.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of (4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine (254 mg, 0.798 mmol) in dichloroethane (5 mL) under nitrogen atmosphere were added acetic acid (37 mg, 1.6 mmol), triethylamine (97 mg, 1.6 mmol) and cyclopentanone (10 mg, 1.19 mmol). The mixture was stirred for 30 min at ambient temperature and NaHB(OAc)3 (204 mg, 1.6 mmol) was added at 0° C. After stirring overnight, the reaction mixture was filtered over celite, concentrated in vacuo and purified by column chromatography on silica gel eluting with DCM:MeOH:NH3 (89:10:1) to give the title compound (226 mg, 58%). 1H NMR (400 MHz, CDCl3) δ 7.20 (d, 2H), 6.88H), 4.03 (t, 2H), 3.78-3.73 (m, 2H), 3.59-3.53 (m, 2H), 2.84 (q, 1H), 2.73 (t, 2H), 2.65-2.68 (m, 6H), 2.03-2.12 (m, 4H), 1.84-1.94 (m, 6H), 1.65-1.72 (m, 2H), 1.51-1.58 (m, 2H), 1.41-1.46 (m, 2H), 1.07-1.16 (m, 2H).

Workup

  1. stirringAfter stirring overnight
  2. filtrationthe reaction mixture was filtered over celite
  3. concentrationconcentrated in vacuo
  4. custompurified by column chromatography on silica gel eluting with DCM:MeOH:NH3 (89:10:1)

Sources & evidence

ORD record
ord-dcdaedf0558549bbb00d5f26f4ae75d4
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Linked notes

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