Hydrochloric Acid → 3-[[(1,1-Dimethylethoxy)carbonyl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxylic acid

HRID 1686967Notes

Reaction equation

HRID 1686967 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:15](=[O:16])[CH:14]2[CH:9]1[CH:10]1[CH2:17][CH:13]2[CH:12]=[CH:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:18]1CCCC1.[OH-].[Li+].Cl>O.C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH:9]1[CH:10]2[CH2:17][CH:13]([CH:12]=[CH:11]2)[CH:14]1[C:15]([OH:18])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium Hydroxide2×HCID 8028TetrahydrofuranHCID 57885493HCID 57885493, compound

Product 1

HCID 170393423-[[(1,1-Dimethylethoxy)carbonyl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Combine 4-Oxo-3-aza-tricyclo[4.2.1.0(2,5)]non-7-ene-3-carboxylic acid tert-butyl ester (60.94 g, 0.2590 mol) and Tetrahydrofuran (800 mL, 10 mol) in 2 L Erlenmeyer flask. Addition of 1.00 M of Lithium hydroxide in Water (780 mL) gave a slight exotherm and the flask was cooled during addition of LiOH solution with an ice water bath. The mixture was then warmed to rt following addition and stirred at room temperature overnight. Cooled 0° C. in ice/water bath. Added conc HCl to pH 2. A milky white liquid ensued. The THF was mostly removed by rotovap to give a precipitated solid in the water. This aqueous/solid mixture was diluted with 700 mL of CH2Cl2 and stirred for two hours during which the solid completely dissolved in the organic layer. The aqueous was further extracted with 400 mL of CH2Cl2 and the combined organics were dried (MgSO4), filtered and concentrated to give 3-tert-Butoxycarbonylamino-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid as an off-white solid, put on high vac at 40° C. to remove excess dichloromethane present in the solid sample. (60.40 g, 92%). 1H-NMR (CDCL3, 400 MHz): δ 12.0 (broad absorption, 1H) 6.97 (d, J=10.6 Hz, 1H), 6.20 (s, 1H); 3.96 (t, J=9.6 Hz, 1H), 2.99 (s, 1H), 2.74 (s, 1H), 2.60 (d, J=8.4 Hz, 1H), 2.09 (d, J=9.3 Hz, 1H), 1.66 (d, J=9.4 Hz, 1H), 1.47 (s, 9H).

Workup

  1. customgave a slight exotherm
  2. additionaddition
  3. customThe THF was mostly removed by rotovap
  4. customto give a precipitated solid in the water
  5. stirringstirred for two hours during which the solid
  6. dissolutioncompletely dissolved in the organic layer
  7. extractionThe aqueous was further extracted with 400 mL of CH2Cl2
  8. dry with materialthe combined organics were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b496c356810b4f3d8e0437e44184c54e
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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