Diisopropylamine → 4-{[6-(4-Fluorobenzenesulfonyloxy)benzo-thiazol-2-ylcarbamoyl]methyl}piperidine-1-carboxylic acid tert-butyl ester

HRID 1867966Notes

Reaction equation

HRID 1867966 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[C:9]([O:11][S:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[CH:8]=[CH:7][C:5]=2[N:6]=1.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([CH2:35][C:36](O)=[O:37])[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(NC(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C.O>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([CH2:35][C:36](=[O:37])[NH:1][C:2]2[S:3][C:4]3[CH:10]=[C:9]([O:11][S:12]([C:15]4[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=4)(=[O:13])=[O:14])[CH:8]=[CH:7][C:5]=3[N:6]=2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 1512539[1-(tert-Butoxycarbonyl)piperidin-4-yl]acetic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579808144-Fluorobenzenesulfonic acid 2-aminobenzothiazol-6-yl ester2×

Product 1

HCID 579808314-{[6-(4-Fluorobenzenesulfonyloxy)benzo-thiazol-2-ylcarbamoyl]methyl}piperidine-1-carboxylic acid tert-butyl esterYield 96%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-fluorobenzenesulfonic acid 2-aminobenzothiazol-6-yl ester (intermediate 16) (580 mg, 1.32 mmol), 4-carboxymethylpiperidine-1-car-boxylic acid tert-butyl ester (640 mg, 2.63 mmol), HBTU (1.1 g, 2.9 mmol), and N,N-diisopropylamine (1.2 ml, 6.89 mmol) in 12 ml of dimethylformamide, in a test tube equipped with a magnetic bar, is stirred for 3 days at room temperature. 200 ml of water are added to the reaction medium and the mixture is extracted with ethyl acetate. The organic phase is then washed with water and with saturated sodium chloride solution, and then dried over magnesium sulfate and evaporated. The residue obtained is taken up in ethyl acetate and purified on a Varian flash cartridge containing 50 g of silica of porosity 15-35μ, with a gradient of from 5% to 30% of ethyl acetate in cyclohexane, over 100 minutes. After evaporating off the solvent, 700 mg of 4-{[6-(4-fluorobenzenesulfonyloxy)benzothiazol-2-ylcarbamoyl]methyl}piperidine-1-carboxylic acid tert-butyl ester are obtained (yellow oil) in a yield of 96%.

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe organic phase is then washed with water and with saturated sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. customevaporated
  5. customThe residue obtained
  6. custompurified on a Varian flash cartridge
  7. additioncontaining 50 g of silica of porosity 15-35μ
  8. waitwith a gradient of from 5% to 30% of ethyl acetate in cyclohexane, over 100 minutes
  9. customAfter evaporating off the solvent, 700 mg of 4-{[6-(4-fluorobenzenesulfonyloxy)benzothiazol-2-ylcarbamoyl]methyl}piperidine-1-carboxylic acid tert-butyl ester
  10. customare obtained (yellow oil) in a yield of 96%

Sources & evidence

ORD record
ord-bbcb5074c9b5478b89d43f128986f3f7
Source dataset
uspto-grants-2009_12
Patent number
US07632952B2

Reaction notes

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