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

HRID 418017노트

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HRID 418017 반응식
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

참가 물질

9

반응물 6

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 1140Toluene용매3회

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온도
-5 °C

실험 절차

To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added trimethylamine hydrochloride (0.1 eq), tosyl chloride (1.3 eq) and toluene (5 vols) under a nitrogen atmosphere and the reaction mixture agitated to form an oily slurry. The slurry was cooled to −5° C., then (2R)-1-methoxypropan-2-ol (1.0 eq) was added drop-wise over 30 minutes. Toluene (2.5 vols) was added as a line 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 line 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 reaction 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 reaction 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) then 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 an oil to give the title compound as a dry light brown oil. Yield corrected for assay 93-97%. 1H NMR δ (400 MHz CDCl3): 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).

후처리

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

출처 및 근거

ORD 기록
ord-7357894a281c46279105e883ff4ef37d
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093252B2

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