Acetate → 1-Benzyl-3,4 dihydroxy pyrroldine benzene sulfonic acid salt

HRID 2176952Notes

Reaction equation

HRID 2176952 reaction equation
Br[C:2](O)([OH:7])[CH2:3]CCBr.[CH2:9]([NH2:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(N(C(C)C)CC)(C)C.C([O-])([O-])=O.[K+].[K+].[C:32]([O-:35])(=O)[CH3:33].[C:36]1([S:42]([OH:45])(=[O:44])=[O:43])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>O1CCOCC1.CCOC(C)=O.[I-].[K+]>[C:36]1([S:42]([OH:45])(=[O:44])=[O:43])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[CH2:9]([N:16]1[CH2:33][CH:32]([OH:35])[CH:2]([OH:7])[CH2:3]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

10

Reactant 6

HCID 175AcetateHCID 7371Benzenesulfonic AcidHCID 7504BenzylamineHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 186927211,4-Dibromo butane diol

Product 1

HCID 1317329961-Benzyl-3,4 dihydroxy pyrroldine benzene sulfonic acid saltYield 52%

Reagents, catalysts & solvents 3

HCID 4875Potassium IodideCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

In a 3N 5 L RBF with overhead stirrer and reflux condenser, the DL-1,4-dibromo butane diol (100 g, 403 mmol), benzyl amine (39.7 ml, 363 mmol), potassium iodide (3.35 g, 20.17 mmol) and diisopropylethylamine (DIPEA, 70.3 ml, 403 mmol) were suspended in 500 mL dioxane and heated to 110° C. overnight. After 17 h cooled at 80° C., added 750 mL 1M aqueous K2CO3 and 750 mL ethtyl acetate (EtOAc). Allowed to cool to 23° C. and separated layers. Extracted with 500 mL EtOAc and then dried combined organics over Na2SO4. Filtered and concentrated to 400 mL solution. Added benzene sulfonic acid (38.3 g, 242 mmol) in 200 mL EtOAc slowly over 1 h. After 16 h at 23° C., cooled to 0° C. and filtered. Washed cake with 200 mL methyl tert-butyl ether (MTBE) and then dried under vacuum at 40° C. for 6 h to give 73.8 g of 1 as an off-white solid (52% yield). 1H NMR (400 MHz, CD3OD) δ 7.85 (m, 2H), 7.65-7.41 (m, 8H), 4.42 (m, 2H), 4.28 (m, 2H), 3.79 (dd, J=12.7, 4.2 Hz, 1H), 3.51 (dd, J=12.2, 3.4 Hz, 1H), 3.38 (d, J=12.2 Hz, 1H), 3.25 (d, J=12.7 Hz, 1H).

Workup

  1. temperatureIn a 3N 5 L RBF with overhead stirrer and reflux condenser
  2. temperatureAfter 17 h cooled at 80° C.
  3. temperatureAllowed to cool to 23° C.
  4. customseparated layers
  5. extractionExtracted with 500 mL EtOAc
  6. customdried
  7. filtrationFiltered
  8. concentrationconcentrated to 400 mL solution
  9. temperaturecooled to 0° C.
  10. filtrationfiltered
  11. washWashed cake with 200 mL methyl tert-butyl ether (MTBE)
  12. customdried under vacuum at 40° C. for 6 h

Sources & evidence

ORD record
ord-6340a9b92ef9418c88ec978d322c2182
Source dataset
uspto-grants-2015_06
Patent number
US09067882B2

Reaction notes

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