Triethylamine → HCID 86658347, compound

HRID 521345Notes

Reaction equation

HRID 521345 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C@H:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:11]O.C(N(CC)CC)C.CS(Cl)(=O)=O.[N-:33]=[N+:34]=[N-:35].[Na+]>C(Cl)Cl.CN(C=O)C.O.C(OCC)C>[N:33]([CH2:11][C@@H:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:9][C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[Cl:1])=[N+:34]=[N-:35]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 67438563HCID 67438563, compound

Product 1

HCID 86658347HCID 86658347, compoundYield 59.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-tert-butyl 1-(2,4-dichlorophenyl)-3-hydroxypropan-2-ylcarbamate (50 mg, 0.156 mmol) in DCM (1 mL) was cooled to 0° C. Triethylamine (24 μL, 0.172 mmol) was added, followed by methanesulfonyl chloride (24 μL, 0.312 mmol). The reaction mixture was allowed to warm up slowly to room temperature and was stirred for 4 hours. TLC analysis of the reaction mixture showed no more starting material. Diethyl ether was added, and the precipitate was filtered. The filtrate was concentrated, and the resulting residue was diluted with DMF (0.5 mL), and sodium azide (51 mg, 0.781 mmol) was added. The reaction mixture was heated to 100° C. for 16 hours. LC-MS of mixture showed no more starting material. Water was added (5 mL), and the reaction mixture was extracted with diethyl ether (3×5 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified on silica gel (0%-70% EtOAc/hexanes gradient elution to yield (S)-tert-butyl 1-azido-3-(2,4-dichlorophenyl)propan-2-ylcarbamate as an oil (32 mg, 59%). m/z 345 (M+); 1H NMR (CDCl3) δ (ppm) 7.39 (s, 1H), 7.21-7.17 (m, 2H), 4.71-4.68 (m, 1H), 4.07-4.02 (m, 1H), 3.52-3.38 (m, 2H), 2.95-2.86 (m, 2H), 1.38 (s, 9H).

Workup

  1. filtrationthe precipitate was filtered
  2. concentrationThe filtrate was concentrated
  3. additionwas added
  4. temperatureThe reaction mixture was heated to 100° C. for 16 hours
  5. extractionthe reaction mixture was extracted with diethyl ether (3×5 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified on silica gel (
  11. wash0%-70% EtOAc/hexanes gradient elution

Sources & evidence

ORD record
ord-c936389d21dc43abb7a2b40d89e14f6c
Source dataset
uspto-grants-2016_05
Patent number
US09328091B2

Reaction notes

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