Ammonia → (S)-3-Benzo[1,2,5]thiadiazol-5-yl-2-methyl-propan-1-ol

HRID 988747Notes

Reaction equation

HRID 988747 reaction equation
[Li+].CC([N-]C(C)C)C.C1COCC1.CCCCCCC.CCOCC.N.[N:27]1[S:31][N:30]=[C:29]2[CH:32]=[C:33]([CH2:36][C@H:37]([CH3:52])[C:38](N([C@H](C)[C@H](O)C3C=CC=CC=3)C)=[O:39])[CH:34]=[CH:35][C:28]=12.Cl>C1COCC1>[N:27]1[S:31][N:30]=[C:29]2[CH:32]=[C:33]([CH2:36][C@H:37]([CH3:52])[CH2:38][OH:39])[CH:34]=[CH:35][C:28]=12

Participants

7

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 2724682Lithium diisopropylamideHCID 69710086(s)-3-Benzo[1,2,5]thiadiazol-5-yl-n-[(1r,2r)-2-hydroxy-l-methyl-2-phenyl-ethyl]-2,n-dimethyl-propionamideHCID 86588588THF heptane Et2O

Product 1

HCID 69711262(S)-3-Benzo[1,2,5]thiadiazol-5-yl-2-methyl-propan-1-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2M LDA in THF/heptane/Et2O (147 ml, 0.294 mol) is diluted with 415 ml THF and cooled to 0°. At 5° to 10°, BH3.NH3 (10.05 g, 0.293 mol) is added portionwise. The solution is stirred at 0° for 15 minutes, at room temperature for 15 minutes and then recooled to 0°. Then, a solution of (S)-3-benzo[1,2,5]thiadiazol-5-yl-N-[(1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl]-2,N-dimethyl-propionamide (27.2 g, 0.0736 mol) in THF (120 ml) is added dropwise over 30 minutes. The dark red solution is stirred at 0° for 3 h. 2 N HCl (700 ml) is added at 0° and the mixture stirred at this temperature for 30 minutes. Extraction with EtOAc (400 ml and 200 ml), washing of the organic phases with brine, drying with Na2SO4 and evaporation afford the crude product as a yellow-brown oil. MPLC purification (silicagel, 1 kg, EtOAc/hexane 2:1) yield pure (S)-3-Benzo[1,2,5]thiadiazol-5-yl-2-methyl-propan-1-ol as a yellow oil. ee=93.3% (HPLC on chiral stat. phase). TLC (silicagel, EtOAc/hexanes 2:1): rf 0.6.

Workup

  1. temperaturecooled to 0°
  2. customAt 5° to 10°
  3. customrecooled to 0°
  4. stirringThe dark red solution is stirred at 0° for 3 h
  5. stirringthe mixture stirred at this temperature for 30 minutes
  6. extractionExtraction with EtOAc (400 ml and 200 ml)
  7. washwashing of the organic phases with brine
  8. dry with materialdrying with Na2SO4 and evaporation
  9. customafford the crude product as a yellow-brown oil
  10. customMPLC purification (silicagel, 1 kg, EtOAc/hexane 2:1)

Sources & evidence

ORD record
ord-1f21326f5b364071845f757e6b58c8a2
Source dataset
uspto-grants-2003_10
Patent number
US06635647B2

Reaction notes

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