Citric Acid → 2-(2-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetic Acid

HRID 1964143Notes

Reaction equation

HRID 1964143 reaction equation
[CH:1]([O:4][C:5]1[CH:31]=[CH:30][C:8]([CH2:9][O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]2[CH2:20][CH2:21][CH2:22][CH:23]([CH2:24][C:25]([O:27]CC)=[O:26])[C:15]2=[CH:14]3)=[CH:7][C:6]=1[C:32]([F:35])([F:34])[F:33])([CH3:3])[CH3:2].[Li+].[OH-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(Cl)Cl>O1CCOCC1.CCOC(C)=O>[CH:1]([O:4][C:5]1[CH:31]=[CH:30][C:8]([CH2:9][O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]2[CH2:20][CH2:21][CH2:22][CH:23]([CH2:24][C:25]([OH:27])=[O:26])[C:15]2=[CH:14]3)=[CH:7][C:6]=1[C:32]([F:35])([F:33])[F:34])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 3939Lithium HydroxideHCID 6344DichloromethaneHCID 67248678Ethyl 2-(2-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetate

Product 1

HCID 583296152-(2-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetic AcidYield 106.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 2-(2-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl)acetate (0.147 g, 0.3 mmol) was dissolved in 1,4-dioxane (4.5 mL). LiOH (1.0 M, 1.501 mL) was added at 25° C. to give a slightly turbid solution. The reaction was heated at 50° C. for 2 h, cooled to 24° C., and acidified with 0.5 M citric acid (6.01 mL, 3.00 mmol). The mixture was diluted with EtOAc (50 mL), washed with water (2×10 mL), brine (10 mL), and dried over MgSO4. The solvent was evaporated in vacuo to give an oil which was coevaporated with DCM and hexanes (excess) at 25° C. to give the title compound as an off-white solid (147 mg). LCMS m/z=462.1 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.28 (d, J=6.06 Hz, 6H), 1.39-1.57 (m, 1H), 1.83-2.20 (m, 3H), 2.40-2.48 (m, 2H), 2.84 (dd, J=15.85, 5.62 Hz, 1H), 3.73-3.86 (m, 1H), 4.11 (m, 1H), 4.78 (dt, J=12.16, 6.11 Hz, 1H), 5.06 (s, 2H), 6.15 (s, 1H), 6.78 (dd, J=8.72, 2.40 Hz, 1H), 7.05 (d, J=2.40 Hz, 1H), 7.23 (d, J=8.72 Hz, 1H), 7.29 (d, J=9.22 Hz, 1H), 7.63-7.70 (m, 2H), 12.27 (bs, 1H).

Workup

  1. customto give a slightly turbid solution
  2. temperaturecooled to 24° C.
  3. washwashed with water (2×10 mL), brine (10 mL)
  4. dry with materialdried over MgSO4
  5. customThe solvent was evaporated in vacuo
  6. customto give an oil which

Sources & evidence

ORD record
ord-aa5a07b7f63945e9a27d419a6b38690e
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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