Triethylamine → HCID 11748880, compound

HRID 1985936Notes

Reaction equation

HRID 1985936 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

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27339255-Chlorothiophene-2-sulfonyl chlorideHCID 86594489HCID 86594489, compound

Product 1

HCID 11748880HCID 11748880, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (2S,3R)-2-amino-3-ethyl-5,5,5-trifluoropentan-1-ol (120 mg, 0.701 mmol), triethylamine (0.1 mL, 1.4 mmol) and methylene chloride (50 mL) cooled to 0° C., was added 5-chlorothiophene-2-sulfonyl chloride (220 mg, 0.841 mmol) as a solution in methylene chloride (5 mL), dropwise. After 15 min, the ice bath was removed and the reaction was allowed to attain 25° C. overnight. Additional methylene chloride (15 mL) was added and the reaction mixture was poured 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 (0.36 g) that was purified by flash chromatography using ethyl acetate-hexane, 1-4 as eluent. This provided the title compound 5-chloro-N-[(1S,2R)-2-ethyl-4,4,4-trifluoro-1-(hydroxymethyl)butyl]thiophene-2-sulfonamide as an oil (125 mg, 53%). The oil (125 mg) was further purified by prep-chiral HPLC [SFC; AD, 25×0.46 cm; mobile phase, 8:2 hexane-ipa (1 mL/min)] to obtain 5-chloro-N-[(1S,2R)-2-ethyl-4,4,4-trifluoro-1-(hydroxymethyl)butyl]thiophene-2-sulfonamide as a white crystalline solid (0.15 mg, 6.4%, chiral purity 100%, 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. additionthe reaction mixture was poured into saturated sodium bicarbonate solution (25 mL)
  5. customThe organic phase was separated
  6. washwashed sequentially with 1N HCl solution, H2O, brine
  7. dry with materialdried over MgSO4
  8. filtrationThe organic phase was filtered
  9. customevaporated
  10. customto produce a crude oil (0.36 g) that
  11. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-3f918e77d88842fd94ba14b8cc8138c4
Source dataset
uspto-grants-2009_06
Patent number
US07547725B2

Reaction notes

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