Hydrochloric Acid → (R)-1-Methoxypropan-2-yl 4-methylbenzenesulfonate

HRID 658425Notes

Reaction equation

HRID 658425 reaction equation
Cl.CN(C)C.[S:6](Cl)([C:9]1[CH:15]=[CH:14][C:12]([CH3:13])=[CH:11][CH:10]=1)(=[O:8])=[O:7].[CH3:17][O:18][CH2:19][C@H:20]([OH:22])[CH3:21].C(N(CC)CC)C.CN(C)CCCN.Cl>O.C1(C)C=CC=CC=1>[CH3:13][C:12]1[CH:14]=[CH:15][C:9]([S:6]([O:22][C@H:20]([CH3:21])[CH2:19][O:18][CH3:17])(=[O:8])=[O:7])=[CH:10][CH:11]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 7993N,N-Dimethyl-1,3-propanediamineHCID 8471TriethylamineHCID 2733589(R)-(-)-1-Methoxy-2-propanolHCID 10313079Trimethylamine Hydrochloride

Product 1

HCID 12700775(R)-1-Methoxypropan-2-yl 4-methylbenzenesulfonate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent3×

Procedure

To a flask was added under a nitrogen atmosphere trimethylamine hydrochloride (0.1 eq), tosyl chloride (1.3 eq) and toluene (5 vols) and the reaction mixture agitated to form an oily slurry. The slurry was cooled to −5° C. (2R)-1-Methoxypropan-2-ol (1.0 eq) was added drop-wise over 30 minutes. Toluene (2.5 vols) was added as a wash followed by triethylamine (1.5 eq), which was added drop-wise via addition funnel over 30 minutes maintaining the reaction temperature <8° C. Further toluene (2.5 vols) was added as a wash and the reaction mixture held at −5° C. to 5° C. for 4.5 hours. N,N-Dimethyl-1,3-propane-diamine (0.3 eq) was added over 10 minutes at −5° C. The mixture was agitated at −5° C. to 5° C. for 30 minutes. Then 2N hydrochloric acid (0.55 eq) and 70 ml water were added. The mixture was agitated for 30 minutes at 22° C. and the aqueous layer was separated off and discarded. The mixture was washed twice more with water (10 vols each wash) and after separation of the aqueous wash, the toluene layer was distilled to an oil on the rotary evaporator. Toluene (20 vols) was added to the oil and the solution evaporated to give the title compound as a dry light brown oil. Yield (corrected for assay) 93-97%. 1H NMR (400 MHz CDCl3): δ 7.78-7.75 (d, 2H), 7.45-7.43 (d, 2H), 4.66-4.62 (m, 1H), 3.35-3.26 (m, 2H), 3.16 (s, 3H), 2.4 (s, 3H), 1.13-1.11 (d, 3H)

Workup

  1. customto form an oily slurry
  2. additionwas added drop-wise over 30 minutes
  3. additionwas added drop-wise
  4. additionvia addition funnel over 30 minutes
  5. temperaturemaintaining the reaction temperature <8° C
  6. washa wash
  7. stirringThe mixture was agitated at −5° C. to 5° C. for 30 minutes
  8. stirringThe mixture was agitated for 30 minutes at 22° C.
  9. customthe aqueous layer was separated off
  10. washThe mixture was washed twice more with water (10 vols
  11. washeach wash) and
  12. customafter separation of the aqueous wash
  13. distillationthe toluene layer was distilled to an oil on the rotary evaporator
  14. additionToluene (20 vols) was added to the oil
  15. customthe solution evaporated

Sources & evidence

ORD record
ord-a6a63514f5f74fcdac128bcb647ca680
Source dataset
uspto-grants-2011_12
Patent number
US08076481B2

Reaction notes

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