Trifluoroacetic acid → 3-Methyl-2-(1,3,4,9-tetrahydro-beta-carboline-2-sulfonylmethyl)-butyric acid

HRID 992430Notes

Reaction equation

HRID 992430 reaction equation
C([O:5][C:6](=[O:16])[CH:7]([CH2:11][S:12](Cl)(=[O:14])=[O:13])[CH:8]([CH3:10])[CH3:9])(C)(C)C.[CH2:17]1[C:22]2[NH:23][C:24]3[C:29]([C:21]=2[CH2:20][CH2:19][NH:18]1)=[CH:28][CH:27]=[CH:26][CH:25]=3.C(N(CC)CC)C.FC(F)(F)C(O)=O>ClCCl.ClCCl.CO>[CH3:10][CH:8]([CH3:9])[CH:7]([CH2:11][S:12]([N:18]1[CH2:19][CH2:20][C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[NH:23][C:22]=2[CH2:17]1)(=[O:13])=[O:14])[C:6]([OH:5])=[O:16]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 107838Tetrahydro-beta-carbolineHCID 212590942-Chlorosulfonylmethyl-3-methyl-butyric acid tert-butyl ester

Product 1

HCID 98847773-Methyl-2-(1,3,4,9-tetrahydro-beta-carboline-2-sulfonylmethyl)-butyric acidYield 19%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of 2-chlorosulfonylmethyl-3-methylbutyric acid tert-butyl ester (271 mg) in dichloromethane (5 ml) was added to a mixture of 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole (172 mg) and triethylamine (0.42 ml) in dichloromethane (10 ml) at room temperature. The mixture was stirred for 2 h before addition of trifluoroacetic acid (2.4 ml), and stirring continued for a further 2 h. The mixture was evaporated to dryness and the residue partitioned between 1M aqueous sodium hydroxide (15 ml) and diethyl ether (15 ml). The organics were extracted with 1M sodium hydroxide (15 ml). The combined aqueous portions were acidified to pH=5 with 10% citric acid and extracted with ethyl acetate (4×20 ml). The combined organics were washed with water (2×10 ml) and brine (10 ml), then dried (MgSO4), filtered and the solvent removed under reduced pressure to give, after chromatography (SiO2, 20:1 dichloromethane-methanol), the title compound (66 mg, 19%) as a white foam.

Workup

  1. customThe mixture was evaporated to dryness
  2. customthe residue partitioned between 1M aqueous sodium hydroxide (15 ml) and diethyl ether (15 ml)
  3. extractionThe organics were extracted with 1M sodium hydroxide (15 ml)
  4. extractionextracted with ethyl acetate (4×20 ml)
  5. washThe combined organics were washed with water (2×10 ml) and brine (10 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customto give

Sources & evidence

ORD record
ord-0ac7e5117dd44be197e2d27716eda9dd
Source dataset
uspto-grants-2002_10
Patent number
US06469020B2

Reaction notes

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