Ethanol → Trifluoroacetic acid

HRID 1036408Notes

Reaction equation

HRID 1036408 reaction equation
[CH3:1][C@@:2]1([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH:19]4[CH2:24][CH2:23][CH:22]([C:25]([F:28])([F:27])[F:26])[CH2:21][CH2:20]4)[CH:14]=3)[CH:9]=2)[CH2:6][O:5]C(=O)[NH:3]1.C(O)C.[OH2:32].[OH-:33].[Li+]>O>[NH2:3][C@@:2]([C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH:19]3[CH2:24][CH2:23][CH:22]([C:25]([F:26])([F:27])[F:28])[CH2:21][CH2:20]3)[CH:14]=2)[CH:9]=1)([CH3:1])[CH2:6][OH:5].[C:22]([OH:33])([C:25]([F:28])([F:27])[F:26])=[O:32]

Participants

6

Reactant 3

HCID 702EthanolHCID 168937Lithium hydroxide, monohydrateHCID 67412717(R)-4-methyl-4-(6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)oxazolidin-2-one

Product 2

HCID 6422Trifluoroacetic acidHCID 46196225(R)-2-amino-2-(6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

(R)-4-methyl-4-(6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)oxazolidin-2-one (0.1442 g, 0.0003665 mol) was dissolved in ethanol (1.00 mL, 0.0171 mol) in a capped vial equipped with a magnetic stir bar. 4.2 M Lithium hydroxide, monohydrate in water (1.00 mL) was added and the mixture was heated overnight at 80° C. with stirring. TLC analysis showed that the reaction was complete. The mixture was concentrated to dryness under vacuum. Water (3 mL) and methylene chloride (3 mL) were added and the layers were separated (2×). The combined organic layers were concentrated under vacuum and purified by HPLC to give the title compound as a TFA salt in 0.0388 g (29% yield). MS: m/z=351.41 [M−NH2]+. 1H NMR (400 MHz, MeOD) δ 1.48-1.65 (m, 2H), 1.75-1.80 (m, 4H), 2.04-2.11 (m, 2H), 2.17-2.25 (m, 2H), 2.33 (d, J=11.04 Hz, 2H), 3.79-3.85 (m, 1H), 3.90-3.95 (m, 1H), 4.41-4.83 (m, 1H, 2:1 ratio), 7.16-7.27 (m, 1H, 2:1 ratio) 7.29-7.32 (m, 1H), 7.52 (dd, J=8.66, 2.13 Hz, 1H), 7.79-7.88 (m, 3H)

Workup

  1. customvial equipped with a magnetic stir bar
  2. concentrationThe mixture was concentrated to dryness under vacuum
  3. additionWater (3 mL) and methylene chloride (3 mL) were added
  4. customthe layers were separated (2×)
  5. concentrationThe combined organic layers were concentrated under vacuum
  6. custompurified by HPLC

Sources & evidence

ORD record
ord-c14f23bc077344feae7e517ad339c949
Source dataset
uspto-grants-2013_10
Patent number
US08546359B2

Reaction notes

Loading…