Water → HCID 59369849, compound

HRID 1662098Notes

Reaction equation

HRID 1662098 reaction equation
O[CH2:2][C@H:3]1[N:8]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:7][C@@H:6]2[C@H:4]1[CH2:5]2.C([N:21](CC)CC)C.CS(Cl)(=O)=O.[N-]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>ClCCl>[NH2:21][CH2:2][C@H:3]1[N:8]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:7][C@@H:6]2[C@H:4]1[CH2:5]2

Participants

8

Reactant 6

HCID 962WaterHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 59369842HCID 59369842, compound

Product 1

HCID 59369849HCID 59369849, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of racemic 7-2 (9.6 g, 38.8 mmol) in dichloromethane (190 mL) at 0° C. was added triethylamine (7.86 g, 78.0 mmol) followed by methanesulfonyl chloride (6.67 g, 58.2 mmol) and the reaction mixture was slowly warmed to ambient temperature over 24 h. The mixture was then quenched with water and extracted with dichloromethane. The combined organic layers were dried over MgSO4 and concentrated to an oil. The residue was dissolved in dimethylformamide (100 mL) and to this mixture was added sodium azide (10.1 g, 155 mmol). The reaction mixture was heated to 90° C. for 15 h. The reaction was cooled and partition between EtOAc (300 mL) and water (100 mL). The organic phase was washed with water (3×100 mL), and the organic phase was dried over MgSO4 and concentrated to an oil. The oil was dissolved in THF (370 mL) and to this was added polymer-bound triphenylphosphine (18.4 g, 40.4 mmol, 2.2 mmol/g loading) and water (6.6 g, 367 mmol). The reaction was heated to 50° C. for 2 h and the reaction was complete. The reaction was cooled to ambient temperature dried over MgSO4 and concentrated to yield >80% pure product as an oil which was used as is in the next reaction. ESI+ MS: [M+H]+ 247.4.

Workup

  1. customThe mixture was then quenched with water
  2. extractionextracted with dichloromethane
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated to an oil
  5. dissolutionThe residue was dissolved in dimethylformamide (100 mL) and to this mixture
  6. temperatureThe reaction mixture was heated to 90° C. for 15 h
  7. temperatureThe reaction was cooled
  8. custompartition between EtOAc (300 mL) and water (100 mL)
  9. washThe organic phase was washed with water (3×100 mL)
  10. dry with materialthe organic phase was dried over MgSO4
  11. concentrationconcentrated to an oil
  12. dissolutionThe oil was dissolved in THF (370 mL)
  13. temperatureThe reaction was heated to 50° C. for 2 h
  14. temperatureThe reaction was cooled to ambient temperature
  15. dry with materialdried over MgSO4
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-30ad1e7f6b034b51a99fcbbce8481fbd
Source dataset
uspto-grants-2011_10
Patent number
US08030495B2

Reaction notes

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