Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 23072461, compound

HRID 1182454Notes

Reaction equation

HRID 1182454 reaction equation
[CH3:1][C:2]([CH3:21])([CH:10]([O:19][CH3:20])[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)[CH2:3][CH2:4][CH2:5][CH2:6][C:7](O)=[O:8].Cl.CN(C)CCCN=C=NCC.O.[OH:35][N:36]1C2C=CC=CC=2N=N1.NOC1CCCCO1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>CN(C=O)C>[OH:35][NH:36][C:7](=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][C:2]([CH3:21])([CH3:1])[CH:10]([O:19][CH3:20])[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1

Participants

7

Reactant 5

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 23072370HCID 23072370, compound

Product 1

HCID 23072461HCID 23072461, compoundYield 199.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the carboxylic acid from step 1 (100 mg, 0.344 mmol), in DMF (10 mL) at room temperature were added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 79 mg, 0.414 mmol) and 1-hydroxybenzotriazole hydrate (HOBt, 70 mg, 0.516 mmol). The mixture was stirred for 20 min. at room temperature, and then NH2OTHP (60 mg, 0.516 mmol) was added. The resulting mixture was heated overnight at 50° C., and then concentrated. The crude material was dissolved in CH2Cl2 and washed with a saturated aqueous solution of NaHCO3. The aqueous layer was extracted several times with CH2Cl2 and the combined organic extracts were dried over anhydrous MgSO4 and concentrated. The crude material was purified by flash chromatography using hexane/acetone (7:3) as the solvent mixture. The pure protected hydroxamate was then dissolved in MeOH (10 mL), and 10-camphorsulfonic acid (CSA, 40 mg, 0.172 mmol) was added. The mixture was stirred for 2 h at room temperature, and then the solvents were evaporated under reduced pressure at room temperature to avoid thermal decomposition. The crude mixture was purified by flash chromatography using CH2Cl2/MeOH (9:1) as the solvent mixture, giving compound 28 as colorless oil (212 mg, 68%): 1H NMR: (300 MHz, d6-acetone) δ 7.18 (d, J=8 Hz, 2H), 6.89 (d, J=8 Hz, 2H), 3.85 (s, 1H), 3.79 (s, 3H), 3.11 (s, 3H), 2.11-2.05 (m, 2H), 1.45 (br. s, 2H), 1.34 (br. s, 4H), 0.83 (s, 3H), 0.76 (s, 3H).

Workup

  1. temperatureThe resulting mixture was heated overnight at 50° C.
  2. concentrationconcentrated
  3. dissolutionThe crude material was dissolved in CH2Cl2
  4. washwashed with a saturated aqueous solution of NaHCO3
  5. extractionThe aqueous layer was extracted several times with CH2Cl2
  6. dry with materialthe combined organic extracts were dried over anhydrous MgSO4
  7. concentrationconcentrated
  8. customThe crude material was purified by flash chromatography
  9. dissolutionThe pure protected hydroxamate was then dissolved in MeOH (10 mL)
  10. stirringThe mixture was stirred for 2 h at room temperature
  11. customthe solvents were evaporated under reduced pressure at room temperature
  12. customThe crude mixture was purified by flash chromatography

Sources & evidence

ORD record
ord-3d66e7a35ee24662a3ed09b264da45f4
Source dataset
uspto-grants-2007_10
Patent number
US07288567B2

Reaction notes

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