Hydrochloric Acid → Trifluoroacetic acid

HRID 1942313Notes

Reaction equation

HRID 1942313 reaction equation
[CH3:1][C:2]([CH3:34])([CH3:33])[CH2:3][CH2:4][C@@H:5]([N:12]1[CH2:17][CH2:16][CH2:15][C@H:14]([CH2:18][C:19]([O:21]C)=[O:20])[C@H:13]1[C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1)[CH2:6][CH2:7][C:8]([F:11])([F:10])[F:9].[OH-:35].[K+].Cl.[CH3:38][OH:39]>>[CH3:1][C:2]([CH3:34])([CH3:33])[CH2:3][CH2:4][C@@H:5]([N:12]1[CH2:17][CH2:16][CH2:15][C@H:14]([CH2:18][C:19]([OH:21])=[O:20])[C@H:13]1[C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:25][CH:24]=1)[CH2:6][CH2:7][C:8]([F:9])([F:10])[F:11].[C:38]([OH:39])([C:8]([F:11])([F:10])[F:9])=[O:35]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887Methanol2×HCID 14797Potassium HydroxideHCID 86639345HCID 86639345, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 59201225HCID 59201225, compound

Conditions

Temperature
60 °C

Procedure

A solution of methyl {(2S,3R)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-3-yl}acetate (3.9 g) in methanol (50 mL) was treated with 1M potassium hydroxide in methanol (25 mL, 25.0 mmol) was heated to 60° C. for 16 hours. The reaction was treated with 25 mL 1M HCl and partitioned between water and ethyl acetate. The organics were washed with brine, dried over sodium sulfate, filtered and evaporated in vacuo. The reaction was purified by reverse phase chromatography (35-100% acetonitrile/water) to give {(2S,3R)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-3-yl}acetic acid as its TFA salt. This salt was taken up in ethyl acetate and treated with 10 mL concentrated HCl and stirred vigorously for 24 hours. The solution was evaporated in vacuo to give exclusively the HCl salt. 1H NMR (600 MHz, CD3OD: δ 7.80 (bm, 4H), 4.65 (bm, 1H), 3.69 (bm, 1H), 3.22 (bm, 1H), 2.69 (bs, 2H), 2.24 (m, 1H), 2.12 (m, 4H), 2.04 (d, J=8.2 Hz, 1H), 2.01 (d, J=8.2 Hz, 1H), 1.91 (m, 3H), 1.66 (m, 1H), 1.51 (m, 1H), 1.13 (m, 1H), 0.92 (s, 9H), 0.74 (td, J=12.6, 3.8 Hz, 1H); LC/MS (EIMS, M+H)=482.1.

Workup

  1. custompartitioned between water and ethyl acetate
  2. washThe organics were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe reaction was purified by reverse phase chromatography (35-100% acetonitrile/water)

Sources & evidence

ORD record
ord-9b81e7acb3754d23a681448465560b9a
Source dataset
uspto-grants-2013_03
Patent number
US08389547B2

Reaction notes

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