Phenylacetyl chloride → 2-Phenyl-N-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-acetamide

HRID 272894Notes

Reaction equation

HRID 272894 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(N(CC)CC)C.[C:31]1([CH2:37][C:38](Cl)=[O:39])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>ClCCl>[C:31]1([CH2:37][C:38]([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)=[O:39])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 7679Phenylacetyl chlorideHCID 8471TriethylamineHCID 11645410(4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine

Product 1

HCID 598374372-Phenyl-N-{4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-ylmethyl}-acetamideYield 12.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of {4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine (200 mg, 0.63 mmol) and triethylamine (93 μL, 0.66 mmol) in anhydrous dichloromethane (8 mL) under nitrogen atmosphere at 0° C. was added dropwise a solution of phenylacetyl chloride (93 μL, 0.66 mmol) in anhydrous dichloromethane (2 mL). After stirring for 3 h at 0° C., the reaction mixture was quenched with a saturated aqueous solution of NaHCO3. The organic layer was separated and washed with water then dried over magnesium sulfate, filtered, concentrated under reduced pressure and purified by column chromatography on silica gel eluting with DCM:MeOH (98:2) to give the title compound (34 mg, 12%). 1H NMR (400 MHz, CDCl3) δ7.32-7.31 (m, 3H), 7.12-7.10 (m, 2H), 6.89-6.87 (d, 2H), 6.76-6.74 (d, 2H), 4.91 (t, 1H), 4.02 (t, 2H), 3.79-3.74 (m, 2H), 3.53-3.51 (m, 2H), 3.47 (s, 2H), 3.37-3.35 (d, 2H), 2.62 (m, 6H), 2.08-2.06 (m, 2H), 1.93-1.85 (m, 6H), 1.76-1.74 (m, 2H).

Workup

  1. customthe reaction mixture was quenched with a saturated aqueous solution of NaHCO3
  2. customThe organic layer was separated
  3. washwashed with water
  4. dry with materialthen dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by column chromatography on silica gel eluting with DCM:MeOH (98:2)

Sources & evidence

ORD record
ord-dbf08d2c57d14acba54bdf16b2beff2c
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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