tert-Butyl methyl ether → (R)-1-(3-chlorothien-2-yl)-2-butyltoluenesulfonamide lithium salt

HRID 365939Notes

Reaction equation

HRID 365939 reaction equation
[Cl:1][C:2]1[CH:6]=[CH:5][S:4][CH:3]=1.[CH2:7]([Li:11])[CH2:8][CH2:9][CH3:10].[C:12]1(C)[CH:17]=[CH:16][C:15]([S:18]([N:21]2C[C@H]2CC)(=[O:20])=[O:19])=[CH:14][CH:13]=1.[CH3:27]C(OC)(C)C>>[Li+:11].[Cl:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C@@:14]1([CH3:27])[CH:13]=[CH:12][CH:17]=[CH:16][C:15]1([CH2:7][CH2:8][CH2:9][CH3:10])[S:18]([NH-:21])(=[O:19])=[O:20]

Participants

5

Reactant 4

HCID 15413tert-Butyl methyl ether2×HCID 870173-ChlorothiopheneHCID 110096371-p-Toluenesulfonyl-2(r)-ethylaziridineHCID 178418339Butyllithium

Product 1

HCID 131722022(R)-1-(3-chlorothien-2-yl)-2-butyltoluenesulfonamide lithium salt

Conditions

Temperature
-5 °C

Procedure

Under a nitrogen atmosphere, a solution of 3-chlorothiophene (48.75 g) in TBME (291 g) is cooled to -10° C. and 2.5 M n-butyllithium in hexanes (151.3 mL) is added at such a rate that the reaction temperature is maintained between 0 and 5° C. After the addition is complete, the mixture is cooled to -5° C. and 1-p-toluenesulfonyl-2(R)-ethylaziridine (74.1 g, as a 56.9 % (w/w) solution in TBME) is added at such a rate as to maintain the temperature of the reaction mixture below 9° C. (during which time a solid precipitates). After about 5 minutes, the mixture is cooled to 0° C. and the precipitate is collected by vacuum filtration, washed with 0° C. TBME (60 mL), and dried in vacuo at about 40° C., to give (R)-1-(3-chlorothien-2-yl)-2-butyltoluenesulfonamide lithium salt. m.p. 372° C. (dec.). MS (FAB), m/z 350, 352 (100%), 1HNMR (200 Mhz, DMSO) δ 0.8 (t, 3H): 2.25 (s, 3H); 6.85 (d, 1H); 7.05 (d, 2H), 7.35 (d, 2H).

Workup

  1. temperatureis maintained between 0 and 5° C
  2. additionAfter the addition
  3. temperatureto maintain the temperature of the reaction mixture below 9° C. (during which time a solid
  4. customprecipitates)
  5. temperaturethe mixture is cooled to 0° C.
  6. filtrationthe precipitate is collected by vacuum filtration
  7. washwashed with 0° C
  8. dry with materialTBME (60 mL), and dried in vacuo at about 40° C.

Sources & evidence

ORD record
ord-288fde99672c4208b19bc06be41cd6f8
Source dataset
uspto-grants-2000_10
Patent number
US06127550

Reaction notes

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