Acetic Acid → 5-Bromo-6-hydroxymethyl-3,3a,7,7a-tetrahydro-1H-4-thia-2-aza-cyclopenta[alpha]pentalene-2-carboxylic acid ethyl ester

HRID 1013358Notes

Reaction equation

HRID 1013358 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:13][CH:12]2[CH:8]([CH2:9][C:10]3[C:16]([CH2:17][OH:18])=[CH:15][S:14][C:11]=32)[CH2:7]1)=[O:5])[CH3:2].CC(O)=O.C1C(=O)N([Br:30])C(=O)C1>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]([N:6]1[CH2:13][CH:12]2[CH:8]([CH2:9][C:10]3[C:16]([CH2:17][OH:18])=[C:15]([Br:30])[S:14][C:11]=32)[CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 67184N-bromobutanimideHCID 58624945HCID 58624945, compound

Product 1

HCID 1317290265-Bromo-6-hydroxymethyl-3,3a,7,7a-tetrahydro-1H-4-thia-2-aza-cyclopenta[alpha]pentalene-2-carboxylic acid ethyl esterYield 36%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of the product from Example 17, step c) (199 mg, 0.79 mmol) in CHCl3 (3 ml) and AcOH (3 ml) was added NBS (156 mg, 0.88 mmol). The reaction mixture was stirred for 30 minutes, quenched with saturated NaHCO3 (10 ml), and extracted with EtOAc (20 ml). The EtOAc layer was dried (MgSO4), filtered, and solvent evaporated in vacuo to give the crude product that was purified by silica-gel preparative TLC (hexanes:EtOAc-3:1) providing the subtitle compound (99.6 mg, 36%). 1H NMR (300 MHz, CDCl3, ppm) 1.22 (t, J=7 Hz, 3H); 2.42 (br s, 1H); 2.63-2.78 (m, 1H); 2.95-3.18 (m, 2H); 3.30-3.48 (br m, 1H); 3.50-3.72 (br m, 2H); 3.75-3.88 (br m, 2H); 4.08 (q, J=7 Hz, 2H); 4.52 (s, 2H).

Workup

  1. customquenched with saturated NaHCO3 (10 ml)
  2. extractionextracted with EtOAc (20 ml)
  3. dry with materialThe EtOAc layer was dried (MgSO4)
  4. filtrationfiltered
  5. customsolvent evaporated in vacuo
  6. customto give the crude product that
  7. customwas purified by silica-gel preparative TLC (hexanes:EtOAc-3:1)

Sources & evidence

ORD record
ord-e10ffff8fbe44e84ad04fc288d76a781
Source dataset
uspto-grants-2011_07
Patent number
US07981919B2

Reaction notes

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