2-Bromoethanol → 2,2,2-Trifluoro-N-((1-(2-hydroxyethyl)piperidin-4-yl)methyl)-N-(trans-2-phenylcyclopropyl)acetamide

HRID 529295Notes

Reaction equation

[F:1][C:2]([F:23])([F:22])[C:3]([N:5]([C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=[O:4].C(=O)([O-])[O-].[K+].[K+].Br[CH2:31][CH2:32][OH:33]>C(#N)C>[F:23][C:2]([F:1])([F:22])[C:3]([N:5]([CH2:6][CH:7]1[CH2:8][CH2:9][N:10]([CH2:31][CH2:32][OH:33])[CH2:11][CH2:12]1)[C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:4]

Participants

Conditions

Temperature: 80 °C

Procedure

To the solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (60 mg, 0.184 mmol) in acetonitrile (10 mL) was added potassium carbonate (76 mg, 0.552 mmol) followed by 2-bromoethanol (29.9 mg, 0.239 mmol). The reaction mixture was heated in the seal tube at 80° C. for 4 hours. The reaction mixture was then filtered and evaporated. 2,2,2-Trifluoro-N-((1-(2-hydroxyethyl)piperidin-4-yl)methyl)-N-(trans-2-phenylcyclopropyl)acetamide (40 mg, 0.103 mmol, 55.8% yield) was isolated as yellow oil. 1H NMR (400 MHz, METHANOL-d4) δ 7.07-7.37 (m, 5H), 3.75-3.87 (m, 2H), 3.57-3.66 (m, 1H), 3.49-3.57 (m, 1H), 3.46 (t, J=6.06 Hz, 1H), 3.36-3.41 (m, 3H), 3.19 (t, J=3.79 Hz, 1H), 2.78-3.04 (m, 2H), 2.56-2.76 (m, 1H), 2.48 (ddd, J=3.54, 6.51, 10.17 Hz, 1H), 1.96-2.15 (m, 1H), 1.87 (td, J=2.91, 10.80 Hz, 2H), 1.63 (dt, J=5.24, 10.23 Hz, 1H), 1.39-1.57 (m, 3H); LC-MS Rt=0.76 min; MS (ESI): 371.2 [M+H]+.

Workup

filtrationThe reaction mixture was then filtered
customevaporated

Sources & evidence

ORD record: ord-a9cb128e44f74267b5b568bba916fec5
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346840B2

Reaction notes

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