Trifluoroacetic acid → cis-4-(4-(Benzyloxy)phenyl)-3-fluoropiperidine

HRID 1507266Notes

Reaction equation

HRID 1507266 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15]2[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][C@H:16]2[F:28])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15]2[CH2:20][CH2:19][NH:18][CH2:17][C@H:16]2[F:28])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118217219cis-Tert-butyl 4-(4-(benzyloxy)phenyl)-3-fluoropiperidine-1-carboxylate

Product 1

HCID 118207456cis-4-(4-(Benzyloxy)phenyl)-3-fluoropiperidineYield 91.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of cis-tert-butyl 4-(4-(benzyloxy)phenyl)-3-fluoropiperidine-1-carboxylate (400 mg, 1.04 mmol) in CH2Cl2 (4 mL) was dropwise added TFA (1 mL, 13 mmol) at rt. The mixture was stirred at rt for 2 h and then concentrated. To the residue was added 50 mL of saturated aqueous sodium bicarbonate and the mixture was extracted with 3×60 mL of CH2Cl2. The organic layer was dried over Na2SO4, filtered, and concentrated to dryness to yield 270 mg cis-4-(4-(benzyloxy)phenyl)-3-fluoropiperidine (0.95 mmol, 91%). (M+H)+=286.25. 1H NMR (500 MHz, chloroform-d) δ 7.49-7.38 (m, 4H), 7.34 (t, J=7.5 Hz, 1H), 7.26-7.20 (m, J=8.5 Hz, 2H), 7.01-6.93 (m, 2H), 5.08 (s, 2H), 4.70 (d, J=49.0 Hz, 1H), 3.38 (t, J=12.5 Hz, 1H), 3.25 (dt, J=13.4, 2.0 Hz, 1H), 2.93 (d, J=14.3 Hz, 1H), 2.90-2.68 (m, 3H), 2.09 (qd, J=12.9, 4.1 Hz, 1H), 1.69 (d, J=14.3 Hz, 1H).

Workup

  1. customat rt
  2. concentrationconcentrated
  3. additionTo the residue was added 50 mL of saturated aqueous sodium bicarbonate
  4. extractionthe mixture was extracted with 3×60 mL of CH2Cl2
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-96dcee6e57f94ece8732da9991e17574
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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