Trifluoroacetic acid → (1,1-Dioxo-1lambda6-thiomorpholin-4-yl)-[1-isopropyl-5-(piperidin-4-yloxy)-1H-indol-2-yl]-methanone

HRID 494008Notes

Reaction equation

HRID 494008 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([CH:24]([CH3:26])[CH3:25])[C:19]([C:27]([N:29]2[CH2:34][CH2:33][S:32](=[O:36])(=[O:35])[CH2:31][CH2:30]2)=[O:28])=[CH:18]3)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[O:36]=[S:32]1(=[O:35])[CH2:33][CH2:34][N:29]([C:27]([C:19]2[N:20]([CH:24]([CH3:25])[CH3:26])[C:21]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:14][CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[CH:23][CH:22]=3)=[O:28])[CH2:30][CH2:31]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 670734974-[2-(1,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl)-1-isopropyl-1H-indol-5-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67073486(1,1-Dioxo-1lambda6-thiomorpholin-4-yl)-[1-isopropyl-5-(piperidin-4-yloxy)-1H-indol-2-yl]-methanoneYield 89.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold (0° C.) mixture of 4-[2-(1,1-dioxo-1λ6-thiomorpholine-4-carbonyl)-1-isopropyl-1H-indol-5-yloxy]-piperidine-1-carboxylic acid tert-butyl ester (410 mg, 1.0 eq.) in dichloromethane (8 mL) was added dropwise trifluoroacetic acid (920 mg, 10 eq.). The mixture was stirred overnight at room temperature then concentrated in vacuo. The residue was partitioned between a potassium carbonate aqueous solution and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over sodium sulfate, filtered and dried in vacuo. The residue was then purified on silica eluting with dichloromethane/methanol/ammoniac 95:5:0.25 v:v:v. to yield 296 mg (86%) of the desired product as off-white oil. MS (m/e): 420.4 (MH+, 100%).

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was partitioned between a potassium carbonate aqueous solution and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. customdried in vacuo
  7. customThe residue was then purified on silica eluting with dichloromethane/methanol/ammoniac 95:5:0.25 v

Sources & evidence

ORD record
ord-58734b1125b64d4db385d3f9b9dcc5be
Source dataset
uspto-grants-2009_05
Patent number
US07538101B2

Reaction notes

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