Diisopropylethylamine → (2R,4R)-1-tert-butyl 2-methyl 4-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)piperidine-1,2-dicarboxylate

HRID 1971299Notes

Reaction equation

HRID 1971299 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[O:28]1[CH2:33][CH2:32][O:31][C:30]2[CH:34]=[C:35]([C:38]([OH:40])=O)[CH:36]=[CH:37][C:29]1=2.CCN(C(C)C)C(C)C.[NH2:50][C@@H:51]1[CH2:56][CH2:55][N:54]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[C@@H:53]([C:64]([O:66][CH3:67])=[O:65])[CH2:52]1>CN(C=O)C.O>[O:28]1[CH2:33][CH2:32][O:31][C:30]2[CH:34]=[C:35]([C:38]([NH:50][C@@H:51]3[CH2:56][CH2:55][N:54]([C:57]([O:59][C:60]([CH3:61])([CH3:62])[CH3:63])=[O:58])[C@@H:53]([C:64]([O:66][CH3:67])=[O:65])[CH2:52]3)=[O:40])[CH:36]=[CH:37][C:29]1=2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 27588331,4-Benzodioxane-6-carboxylic AcidHCID 54209755(2R,4R)-1-tert-butyl 2-methyl 4-aminopiperidine-1,2-dicarboxylate

Product 1

HCID 67266415(2R,4R)-1-tert-butyl 2-methyl 4-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)piperidine-1,2-dicarboxylateYield 95.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

BOP (6.59 g, 14.9 mmol) was added to a solution of 2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylic acid (2.68 g, 14.9 mmol) and DIEA (5.3 mL, 30 mmol) in DMF (50 mL). Then (2R,4R)-1-tert-butyl 2-methyl 4-aminopiperidine-1,2-dicarboxylate (3.5 g, 13.5 mmol) was added to the mixture and the resulting solution was stirred at room temperature for 18 hours. Water (100 mL) was added to quench the reaction, and extracted with ethyl acetate (2×100 mL), organic layers were dried over MgSO4, and concentrated under reduced pressure. The residue was purified by Companion (ReadySep, 120 g, silica gel packed) with ethyl acetate/heptane from 20-50% to give the amide as off-white solid 5.4 g (95%). LC-MC: 421.2 (t=2.4 min).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionextracted with ethyl acetate (2×100 mL), organic layers
  4. dry with materialwere dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by Companion (ReadySep, 120 g, silica gel packed) with ethyl acetate/heptane from 20-50%

Sources & evidence

ORD record
ord-a6918991c82d43aa92c36b7f26eee43a
Source dataset
uspto-grants-2013_04
Patent number
US08431597B2

Reaction notes

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