Hydrochloric Acid → HCID 67264285, compound

HRID 1686939Notes

Reaction equation

HRID 1686939 reaction equation
C([Li])(C)(C)C.[C:6]([O:10][C:11]([N:13]1[CH:22]2[CH2:23][CH2:24][CH:14]1[C:15]1[CH:16]=[C:17]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:18]=[CH:19][C:20]=1[CH2:21]2)=[O:12])([CH3:9])([CH3:8])[CH3:7].B(OC)(OC)[O:34]C.OO.Cl>C1COCC1.CO>[C:6]([O:10][C:11]([N:13]1[CH:22]2[CH2:23][CH2:24][CH:14]1[C:15]1[C:16]([OH:34])=[C:17]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:18]=[CH:19][C:20]=1[CH2:21]2)=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 8470Trimethyl borateHCID 67263367HCID 67263367, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 67264285HCID 67264285, compoundYield 55.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

Tert-butyllithium (1.7M, 2.3 mL, 4.0 mmol) was added dropwise to a solution of 4-tert-butoxycarbonylamino-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-12-carboxylic acid tert-butyl ester (450 mg, 1.2 mmol) in THF (5 mL) at −78° C. The solution was then allowed to warm slowly to −20° C. and stir at that temperature for 1 h before cooling again to −78° C. and adding trimethyl borate (0.37 mL, 3.2 mmol) via syringe. The reaction was allowed to warm to room temperature slowly and stir overnight. The reaction was quenched with methanol (1 mL) and hydrogen peroxide (30% solution, 0.37 mL, 3.6 mmol) was added to the reaction and allowed to stir at room temperature for 2 h. The mixture was then adjusted to neutral pH with 1 N HCl, extracted with CH2Cl2 (3×10 mL), dried over MgSO4, filtered and concentrated. The resulting residue was purified with silica gel chromatography (0-50% EtOAc in hexanes) to obtain 4-tert-Butoxycarbonylamino-3-hydroxy-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-12-carboxylic acid tert-butyl ester as a brown foam (260 mg, 55%). 1HNMR (400 MHz, CDCl3) δ 7.7 (m, 1H), 7.5 (s, 1H), 7.1 (d, 1H, J=8.1 Hz), 6.9 (m, 1H), 4.5 (d, 1H, J=7.8 Hz), 4.1 (m, 1H), 3.1 (dd, 1H, J=14.4, 4.9 Hz), 2.9 (dd, 1H, J=14.4, 4.9 Hz), 2.7 (dd, 1H, J=18.2, 8.1 Hz), 2.6 (dd, 1H, J=18.2, 10.6 Hz), 2.2-2.1 (m, 1H), 1.5-1.3 (m, 19H); 1H-1H COSY interactions between peak at 7.7 and 7.1 ppm; MS (m/e) 391 (M+1).

Workup

  1. temperaturebefore cooling again to −78° C.
  2. temperatureto warm to room temperature slowly
  3. stirringstir overnight
  4. additionwas added to the reaction
  5. stirringto stir at room temperature for 2 h
  6. extractionextracted with CH2Cl2 (3×10 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified with silica gel chromatography (0-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c1f7811bf35a42f9a3c976e497142814
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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