Propyl p-toluenesulfonate → (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine p-TSA

HRID 1897743Notes

Reaction equation

HRID 1897743 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[CH2:10][C@@H:9]([NH2:11])[CH2:8][CH2:7][C:5]=2[N:6]=1.[S:12]([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)([O:15][CH2:16][CH2:17][CH3:18])(=[O:14])=[O:13]>CN(C)C=O.CC(OC)(C)C>[CH2:16]([NH:11][C@@H:9]1[CH2:8][CH2:7][C:5]2[N:6]=[C:2]([NH2:1])[S:3][C:4]=2[CH2:10]1)[CH2:17][CH3:18].[CH3:23][C:22]1[CH:24]=[CH:25][C:19]([S:12]([OH:15])(=[O:14])=[O:13])=[CH:20][CH:21]=1

Participants

5

Reactant 2

HCID 69035Propyl p-toluenesulfonateHCID 115211532,6-Diamino-4,5,6,7-tetrahydrobenzothiazole, (S)-

Product 1

HCID 86623292(6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine p-TSAYield 50%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

A 72 liter unjacketed reactor was charged with 1.84 kg (10.87 mol) of (6R)-2,6 diamino-4,5,6,7-tetrahydro-benzothiazole ((6R) diamine), followed by 14.7 L of dimethyl formamide (DMF). Under continuous stirring, the mixture was heated to a temperature of between 65° C. and 68° C. A solution of 2926 grams propyl tosylate and 1761 grams diisopropylethyleamine in 3.5 L DMF was added slowly over a period of 2 hours. The reaction was continued at 67° C. for an additional 4 hours, after which the solution was gradually cooled to room temperature (18° C. to 22° C.) and stirred for an additional 15 hours. The solution was diluted with 14.7 L of MTBE over a time period of 30 minutes, and stirred for an additional 1 hour. The precipitated material was collected by filtration and washed with 7.3 L MTBE, followed by 3 washes of 3.7 L each of ethanol, and a wash with 9.2 L heptane. The washed precipitated cake was dried under high vacuum at 30° C. to 35° C. The final weight of the dried product was 2090-grams, representing a 50% yield.

Workup

  1. temperatureUnder continuous stirring, the mixture was heated to a temperature of between 65° C. and 68° C
  2. additionwas added slowly over a period of 2 hours
  3. stirringstirred for an additional 1 hour
  4. filtrationThe precipitated material was collected by filtration
  5. washwashed with 7.3 L MTBE
  6. washa wash with 9.2 L heptane
  7. customThe washed precipitated cake
  8. customwas dried under high vacuum at 30° C. to 35° C

Sources & evidence

ORD record
ord-6d39e7a507524adb9f04eab106e62a6d
Source dataset
uspto-grants-2013_08
Patent number
US08519148B2

Reaction notes

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