Trifluoroacetic acid → N-(2-amino-5-(thiophen-2-yl)phenyl)tetrahydro-2H-pyran-4-carboxamide

HRID 2201677Notes

Reaction equation

HRID 2201677 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([NH:9][C:10]2[CH:15]=[C:14]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)[CH:13]=[CH:12][C:11]=2[NH:21]C(=O)OC(C)(C)C)=[O:8])[CH2:3][CH2:2]1.FC(F)(F)C(O)=O>ClCCl>[NH2:21][C:11]1[CH:12]=[CH:13][C:14]([C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)=[CH:15][C:10]=1[NH:9][C:7]([CH:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)=[O:8]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71007312tert-butyl (2-(tetrahydro-2H-pyran-4-carboxamido)-4-(thiophen-2-yl)phenyl)carbamate

Product 1

HCID 71466378N-(2-amino-5-(thiophen-2-yl)phenyl)tetrahydro-2H-pyran-4-carboxamideYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl (2-(tetrahydro-2H-pyran-4-carboxamido)-4-(thiophen-2-yl)phenyl)carbamate in dichloromethane (20 mL) was added trifluoroacetic acid (7 mL) at room temperature. The reaction mixture was stirred at room temperature for 2 h. the solvents were then removed under reduced pressure. A saturated aqueous solution of sodium bicarbonate was added. The product was extracted with EtOAc, washed with water and brine, dried, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, MeOH/CH2Cl2) to afford N-(2-amino-5-(thiophen-2-yl)phenyl)tetrahydro-2H-pyran-4-carboxamide as a beige solid (1.1 g, 86% yield). ESI+ MS: m/z 303 ([M+H]+), 1H NMR (500 MHz, d6-DMSO): δ 9.12 (s, 1H), 7.51 (d, J=2.0 Hz, 1H), 7.34 (d, J=5.0 Hz, 1H), 7.24-7.18 (m, 2H), 7.03 (dd, J=5.5; 3.5 Hz, 1H), 6.75 (d, J=8.5 Hz, 1H), 5.05 (s, 1H), 3.91 (dd, J=11.0; 2.0 Hz, 2H), 3.36 (dt, J=11.0; 2.0 Hz, 2H), 2.68-2.62 (m, 1H), 1.80-1.64 (m, 4H).

Workup

  1. customwere then removed under reduced pressure
  2. additionA saturated aqueous solution of sodium bicarbonate was added
  3. extractionThe product was extracted with EtOAc
  4. washwashed with water and brine
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography (silica gel, MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-19fb5fb6ed7742b28de7508fb00a6fdb
Source dataset
uspto-grants-2016_06
Patent number
US09365498B2

Reaction notes

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