Acetic Acid → 2-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}-4-(trifluoromethyl)phenol

HRID 1798928Notes

Reaction equation

C([BH3-])#N.[CH3:4][C:5]1([N:11]2[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[NH2:18][C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=1[OH:29].C(O)(=O)C>C(Cl)Cl>[CH3:4][C:5]1([N:11]2[CH2:16][CH2:15][CH:14]([NH:18][C:19]3[CH:24]=[C:23]([C:25]([F:26])([F:27])[F:28])[CH:22]=[CH:21][C:20]=3[OH:29])[CH2:13][CH2:12]2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1

Participants

Conditions

Temperature: 100 °C

Procedure

Polymer supported cyanoborohydride (191 mg, 0.82 mmol) was added to a solution of 1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinone (D12, 87 mg, 0.44 mmol), 2-amino-4-(trifluoromethyl)phenol (D7, 74 mg, 0.42 mmol, 4.3 mmol/g) and acetic acid (0.12 mL, 2.09 mmol) in DCM (2.5 mL). The mixture was heated by microwave at 100° C. for 10 min before being filtered and concentrated by rotary evaporation to give a yellow oil, which was purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM) to give 2-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}-4-(trifluoromethyl)phenol (D14, 89 mg, 60%) as an off-white solid.

Workup

filtrationbefore being filtered
concentrationconcentrated by rotary evaporation
customto give a yellow oil, which
customwas purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM)

Sources & evidence

ORD record: ord-75ae5d5d1f0c4c4186c35236c1d7e7f6
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08344000B2

Reaction notes

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