Tert-butyl 4-hydroxypiperidine-1-carboxylate → 4-[4-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-[1,3,5]-triazin-2-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 448576Notes

Reaction equation

HRID 448576 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:14][CH:15]=3)[CH2:10][CH2:9]2)[N:3]=1.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([OH:34])[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].CC(C)([O-])C.[K+]>C1COCC1>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][CH:31]([O:34][C:2]2[N:3]=[C:4]([N:8]3[C:16]4[C:11](=[CH:12][C:13]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:14][CH:15]=4)[CH2:10][CH2:9]3)[N:5]=[CH:6][N:7]=2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

5

Reactant 3

HCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 866501751-(4-Chloro-[1,3,5]-triazin-2-yl)-5-methanesulfonyl-2,3-dihydro-1H-indole

Product 1

HCID 581165964-[4-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-[1,3,5]-triazin-2-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

11a was dissolved in THF. 4-Hydroxy-piperidine-1-carboxylic acid tert-butyl ester (40 mg, 1 eq) and potassium tert-butoxide (22 mg, 1 eq) were added and the mixture was stirred at room temperature for 3 h, then was quenched with water. The mixture was extracted with ethyl acetate twice, and the organic layer was washed with water and dried over sodium sulfate. The solvent was evaporated and the residue taken up in methanol and dichloromethane and purified by preparative HPLC to give 11-1, LCMS 476.2 (MH+), tR=3.68 (Method 6).

Workup

  1. customwas quenched with water
  2. extractionThe mixture was extracted with ethyl acetate twice
  3. washthe organic layer was washed with water
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was evaporated
  6. customdichloromethane and purified by preparative HPLC
  7. customto give 11-1, LCMS 476.2 (MH+), tR=3.68 (Method 6)

Sources & evidence

ORD record
ord-d55f16bee9e744b3984020820e3da049
Source dataset
uspto-grants-2013_07
Patent number
US08481731B2

Reaction notes

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