1,2-Dichloroethane → (R)-Methyl 1-(4-(benzyloxy)-5-methoxy-2-nitrobenzoyl)piperidine-2-carboxylate

HRID 1968499Notes

Reaction equation

HRID 1968499 reaction equation
[C:1]([O:9][C:10]1[C:18]([O:19][CH3:20])=[CH:17][C:13]([C:14]([OH:16])=O)=[C:12]([N+:21]([O-:23])=[O:22])[CH:11]=1)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]1[C:30]([O:32][CH3:33])=[O:31].C(Cl)CCl.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[CH2:1]([O:9][C:10]1[C:18]([O:19][CH3:20])=[CH:17][C:13]([C:14]([N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]2[C:30]([O:32][CH3:33])=[O:31])=[O:16])=[C:12]([N+:21]([O-:23])=[O:22])[CH:11]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 7408456methyl (R)-piperidine-2-carboxylateHCID 594400844-Benzoyloxy-5-methoxy-2-nitro benzoic acid

Product 1

HCID 86644085(R)-Methyl 1-(4-(benzyloxy)-5-methoxy-2-nitrobenzoyl)piperidine-2-carboxylateYield 74%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

4-(benzoyloxy)-5-methoxy-2-nitrobenzoic acid (1.70 g, 5.61 mmol), (R)-methyl piperidine-2-carboxylate (1.05 g, 5.84 mmol), EDC (3.90 g, 20.31 mmo) and DIPEA (1.0 ml, 5.75 mmol) was stirred in 20 ml of DMA over night. The mixture was evaporated, diluted with DCM, washed with washed 1M NaH2PO4/NaCl (conc) and 0.1 M NaHCO3/NaCl (conc) separately. The organic solvent layer was separated and dried over MgSO4, filtered, concentrated and purified on SiO2 chromatography eluted with EtAc/DCM (1:15) to afford 1.772 g (74%) of the title product. 1H NMR (CDCl3) 7.69 (s, 1H), 7.40- 7.38 (m, 2H), 7.35-7.27 (m, 3H), 6.76 (d, 1H), 5.15 (s, 2H), 3.91 (s, 3H), 3.83 (s, 1H), 3.73 (s, 3H), 3.18 (m, 2H), 1.70 (m 2H), 1.47 (m, 4H); 13C NMR 171.89, 171.33, 155.10, 154.78, 148.32, 135.59, 129.05, 128.74, 127.80, 109.66, 109.58, 109.41, 71.63, 56.92, 52.70, 52.19, 45.70, 39.92, 27.29, 26.35, 21.63; MS m/z+ 451.2 (M+Na).

Workup

  1. customThe mixture was evaporated
  2. additiondiluted with DCM
  3. washwashed
  4. washwith washed 1M NaH2PO4/NaCl (conc) and 0.1 M NaHCO3/NaCl (conc) separately
  5. customThe organic solvent layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified on SiO2 chromatography
  10. washeluted with EtAc/DCM (1:15)

Sources & evidence

ORD record
ord-beb0370ee5864d598cce1bd3c570a414
Source dataset
uspto-grants-2013_04
Patent number
US08426402B2

Reaction notes

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