Butyl nitrite → 3-(Dipropylcarbamoyl)benzoic acid

HRID 20943

Reaction equation

HRID 20943 reaction equation
C(O[C@H:5]1[CH2:9][N:8](C(OC(C)(C)C)=O)[C@@H:7]([C:17](O)=O)[CH2:6]1)C=C.Br[C:21]1[CH:22]=[C:23]([CH:27]=[C:28]([C:30]([O:32]C)=O)[CH:29]=1)[C:24]([OH:26])=[O:25].N(O[CH2:37]CCC)=O.C(OC(N1C[C@H](O)C[C@@H]1C(O)=O)=O)(C)(C)C>[Cu](Br)Br.O.C(#N)C>[CH2:7]([N:8]([CH2:9][CH2:5][CH3:6])[C:30]([C:28]1[CH:27]=[C:23]([CH:22]=[CH:21][CH:29]=1)[C:24]([OH:26])=[O:25])=[O:32])[CH2:17][CH3:37]

Participants

8

Reactant 4

HCID 10996Butyl nitriteHCID 688616N-Boc-cis-4-hydroxy-D-prolineHCID 225936413-Bromo-5-(methoxycarbonyl)benzoic acidHCID 67315699(4R)-1-Boc-4-(2-propen-1-yloxy)-D-proline

Product 1

HCID 1827693-(Dipropylcarbamoyl)benzoic acidYield 97%

Reagents, catalysts & solvents 3

HCID 24611Copper bromide (CuBr2)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Step G (2): 3-bromo-5-(methoxycarbonyl)benzoic acid. To a mixture of copper (II) bromide (5.5 g, 24.6 mmol), n-butyl nitrite (3.17 g, 30.75 mmol) and acetonitrile (300 mL) was added 3-amino-5-(methoxycarbonyl)benzoic acid (Step G (1), 4.0 g, 20.5 mmol) in aceonitrile (300 mL) over 30 min at 0° C. and the mixture was warmed up and stirred at rt for 3 h. H2O was added and acetonitrile was removed. Ethyl acetate (600 mL) was added and the mixture was washed with 3N HCl, H2O, dried over Na2SO4, and concentrated in vacuo to give the title compound (97% yield): 1H NMR (CDCl3, 500 MHz) δ ppm 3.96 (3H, s), 8.41 (1H, s), 8.41 (1H, s), 8.67 (1H, m). MS (ESI) (M−H)− 259.02.

Workup

  1. temperaturethe mixture was warmed up
  2. customacetonitrile was removed
  3. additionEthyl acetate (600 mL) was added
  4. washthe mixture was washed with 3N HCl, H2O
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f1e12c8ab4c14f8c9ebf66d37ccca20b
Source dataset
uspto-grants-2010_06
Patent number
US07745470B2

Linked notes

Loading…