p-Toluenesulfonic acid → HCID 54757414, compound

HRID 1782172Notes

Reaction equation

HRID 1782172 reaction equation
C(OC(OCC)CCN)C.C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O[CH:40](OCC)[CH2:41][CH2:42][NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])C.[NH2:54][CH:55]([C:59]1[N:60]([CH2:70][C:71]2[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=2)[C:61](=[O:69])[C:62]2[C:67]([CH3:68])=[N:66][S:65][C:63]=2[N:64]=1)[CH:56]([CH3:58])[CH3:57].C(O[BH3-])(=O)C.[Na+]>C1COCC1.C(O)(=O)C.C1(C)C=CC=CC=1.O>[C:46]([O:45][C:44](=[O:50])[NH:43][CH2:42][CH2:41][CH2:40][NH:54][CH:55]([C:59]1[N:60]([CH2:70][C:71]2[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=2)[C:61](=[O:69])[C:62]2[C:67]([CH3:68])=[N:66][S:65][C:63]=2[N:64]=1)[CH:56]([CH3:58])[CH3:57])([CH3:47])([CH3:48])[CH3:49]

Participants

11

Reactant 6

HCID 6101p-Toluenesulfonic acidHCID 90495Di-tert-butyl dicarbonateHCID 5210291-Amino-3,3-diethoxypropaneHCID 23670382SodiumacetoxyborohydrideHCID 54757413HCID 54757413, compoundHCID 71346567tert-Butyl (3,3-diethoxypropyl)carbamate

Product 1

HCID 54757414HCID 54757414, compoundYield 92%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
45 °C

Procedure

To (3,3-diethoxypropyl)amine (1.00 equiv) in THF (2 volumes) was charged di-t-butyldicarbonate (1.05 equiv) in THF (3 volumes). The reaction was heated to 45° C. and held for ½ h. Analysis showed the disappearance of starting material, and the resulting solution was heated to 65° C. p-Toluene sulphonic acid (0.1 equiv) and water (5 volumes) were charged over 10 mins, heating continued at 65° C. and held for ½ hour. Analysis showed disappearance of tert-butyl (3,3-diethoxypropyl)carbamate. Toluene (15 volumes) charged, layers separated and washed with water (5 volumes). A fraction of the solution obtained (0.95 equivs) was charged to a solution containing 6-(1-amino-2-methyl-propyl)-5-benzyl-3-methyl-5H-isothiazolo[5,4-d]pyrimidin-4-one (method 30) (1 equiv), toluene (5 volumes) and molecular sieves (1 weight equivalent). The reaction mixture was stirred overnight at room temperature until the reaction was complete. THF (2.5 volumes) were charged followed by sodium acetoxyborohydride (2.0 equiv) and the resulting mixture held overnight until reaction was complete. Aqueous acetic acid (20% v/v, 2.5 volumes) were charged over 10 minutes, stirred at room temperature for 10 minutes, filtered and washed with water (2.5 volumes). The layers were separated and the organic layer was concentrated under vacuo at 50° C. Further toluene was charged (2.5 volumes) and the solvent removed. The product was obtained as an orange oil (typical yield 92%). m/z 486 (MH+).

Workup

  1. additionwere charged over 10 mins
  2. temperatureheating
  3. customcontinued at 65° C.
  4. waitheld for ½ hour
  5. customlayers separated
  6. washwashed with water (5 volumes)
  7. customA fraction of the solution obtained (0.95 equivs)
  8. additionwas charged to a solution
  9. customthe resulting mixture held overnight until reaction
  10. stirringstirred at room temperature for 10 minutes
  11. filtrationfiltered
  12. washwashed with water (2.5 volumes)
  13. customThe layers were separated
  14. concentrationthe organic layer was concentrated under vacuo at 50° C
  15. additionFurther toluene was charged (2.5 volumes)
  16. customthe solvent removed
  17. customThe product was obtained as an orange oil (typical yield 92%)

Sources & evidence

ORD record
ord-91f07718005a4de5bb5eea1aa9bfbba0
Source dataset
uspto-grants-2009_03
Patent number
US07498333B2

Reaction notes

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