Triethylamine → HCID 15977280, compound

HRID 1594291Notes

Reaction equation

HRID 1594291 reaction equation
[NH2:1][C@@H:2]([C@@H:5]([CH2:11][CH3:12])[CH2:6][C:7]([F:10])([F:9])[F:8])[CH2:3][OH:4].C(N(CC)CC)C.[Cl:20][C:21]1[S:25][C:24]([S:26](Cl)(=[O:28])=[O:27])=[CH:23][CH:22]=1>C(Cl)Cl>[Cl:20][C:21]1[S:25][C:24]([S:26]([NH:1][C@@H:2]([CH2:3][OH:4])[C@@H:5]([CH2:11][CH3:12])[CH2:6][C:7]([F:8])([F:9])[F:10])(=[O:28])=[O:27])=[CH:23][CH:22]=1.[Cl:20][C:21]1[S:25][C:24]([S:26]([NH:1][C@H:2]([CH2:3][OH:4])[C@@H:5]([CH2:11][CH3:12])[CH2:6][C:7]([F:8])([F:9])[F:10])(=[O:28])=[O:27])=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27339255-Chlorothiophene-2-sulfonyl chlorideHCID 865944911-Pentanol, 2-amino-3-ethyl-5,5,5-trifluoro-, (2S,3S)-

Product 2

HCID 11152782HCID 11152782, compoundHCID 15977280HCID 15977280, compoundYield 98.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (2S, 3S)-2-amino-3-ethyl-5,5,5-trifluoropentan-1-ol (145 mg, 0.78 mmol), triethylamine (0.22 mL, 1.56 mmol) and methylene chloride (5 mL) cooled to 0° C., was added 5-chlorothiophene-2- sulfonyl chloride (225 mg, 0.861 mmol) as a solution in methylene chloride (5 mL), dropwise. After 15 min, the ice bath was removed and the reaction mixture was allowed to attain 25° C. overnight. Additional methylene chloride (15 mL) was added and the reaction was quenched by pouring it into saturated sodium bicarbonate solution (25 mL). The organic phase was separated and washed sequentially with 1N HCl solution, H2O, brine and dried over MgSO4. The organic phase was filtered and evaporated to produce a crude oil (0.250 g) that was purified via flash chromatography, eluent: 1:6 ethyl acetate-hexane. This produced the title compound 5-chloro-N-[(1S, 2S)-2-ethyl-4,4,4-trifluoro-1-(hydroxymethyl)butyl]thiophene-2-sulfonamide as an oil (140 mg, 53.8%). The crude oil was further purified by recrystallization from 1:4 EtOAc-heptane. The mixed solvent system was added to 5-chloro-N-[(1S,2S)-4,4,4-trifluoro-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide, heated to obtain a solution, allowed to cool to 25° C. for 3 h and then stored at 0° C. for 19 h. A crystalline white solid precipitated which was filtered and washed with ice-cold heptane to afford 5-chloro-N-[(1R,2S)-2-ethyl-4,4,4-trifluoro-1-(hydroxymethyl)butyl]thiophene-2-sulfonamide as a white crystalline solid (50 mg, 19.2%, chiral purity 91%, analytical purity 100%). Mass Spectrum (−ESI): 364 (M−H)−.

Workup

  1. customthe ice bath was removed
  2. waitto attain 25° C. overnight
  3. additionAdditional methylene chloride (15 mL) was added
  4. customthe reaction was quenched
  5. additionby pouring it into saturated sodium bicarbonate solution (25 mL)
  6. customThe organic phase was separated
  7. washwashed sequentially with 1N HCl solution, H2O, brine
  8. dry with materialdried over MgSO4
  9. filtrationThe organic phase was filtered
  10. customevaporated
  11. customto produce a crude oil (0.250 g) that
  12. customwas purified via flash chromatography, eluent

Sources & evidence

ORD record
ord-a8506a5c23b14a0a91e4d5d8ea0d8deb
Source dataset
uspto-grants-2007_11
Patent number
US07300951B2

Reaction notes

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