Sulfuric Acid → HCID 67425509, compound

HRID 2096242Notes

Reaction equation

HRID 2096242 reaction equation
C(OC([N:8]1[CH2:11][CH:10]([NH:12][C:13](=[O:28])[CH2:14][NH:15][C:16](=[O:27])[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)[CH2:9]1)=O)(C)(C)C.[OH:29][S:30]([OH:33])(=[O:32])=[O:31].C([O-])(O)=O.[Na+]>CO>[S:30]([OH:33])([OH:32])(=[O:31])=[O:29].[NH:8]1[CH2:11][CH:10]([NH:12][C:13]([CH2:14][NH:15][C:16](=[O:27])[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:24])[F:25])[CH:18]=2)=[O:28])[CH2:9]1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 59361606HCID 59361606, compound

Product 1

HCID 67425509HCID 67425509, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

A 12-L 4-neck round bottom flask equipped with a thermocouple, a mechanical stirrer, a condenser, and a nitrogen inlet adapter was charged with Boc-protected intermediate 5 as prepared in the previous step (434 g; 1.08 mol) and methanol (3.5 L) and the solution was stirred at 20° C. under nitrogen. A solution of 9 M H2SO4 (140 mL; 1.26 mol) was added dropwise over 3 min, and then the mixture was warmed to 60° C. and stirred for 6 h. The reaction was cooled to 40° C. and NaHCO3 (420 g; 5.00 mol) was added as one portion and stirred at 12-16° C. for 1 h. The white solid was removed by filtration and washed with MeOH (200 mL×3) and then discarded after being checked by HPLC. The filtrate (total about 4.0 L) was concentrated at 50° C. under high vacuum (20 mmHg) and chased with MeOH (1 L) once to afford crude title compound, 6, as an off-white foamy solid, which was kept at 0° C. in the dark under N2 and used for futher reaction without additional purification. The structure of compound 6 was confirmed by 1H-NMR.

Workup

  1. customA 12-L 4-neck round bottom flask equipped with a thermocouple, a mechanical stirrer, a condenser, and a nitrogen inlet adapter
  2. additionwas charged with Boc-
  3. temperaturethe mixture was warmed to 60° C.
  4. stirringstirred for 6 h
  5. temperatureThe reaction was cooled to 40° C.
  6. stirringstirred at 12-16° C. for 1 h
  7. customThe white solid was removed by filtration
  8. washwashed with MeOH (200 mL×3)
  9. concentrationThe filtrate (total about 4.0 L) was concentrated at 50° C. under high vacuum (20 mmHg) and chased with MeOH (1 L) once

Sources & evidence

ORD record
ord-abe219e292334f32930ddb17c948b677
Source dataset
uspto-grants-2013_05
Patent number
US08450304B2

Reaction notes

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