Triethylamine → HCID 69287261, compound

HRID 2225282Notes

Reaction equation

HRID 2225282 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][C@@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[C@H:10]([CH2:25]O)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.[CH3:35][S:36](Cl)(=O)=O>C(Cl)Cl>[C:1]([O:5][C:6](=[O:27])[NH:7][C@@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[C@H:10]([CH2:25][S:36][CH3:35])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 68765914tert-butyl (1R,3R,4S)-4-benzyloxycarbonylamino-3-(hydroxymethyl)cyclohexylcarbamate

Product 1

HCID 69287261HCID 69287261, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(1R,3R,4S)-(4-Benzyloxycarbonylamino-3-hydroxymethylcyclohexyl)carbamic acid tert-butyl ester (1.0 g) was dissolved in CH2Cl2 (120 ml) and cooled to 0° C. prior to the addition of Et3N (0.5 mL) and methanesulfonyl chloride (0.55 mL). This mixture was warmed to RT and was stirred for 3 h. The CH2Cl2 was removed and EtOAc was added along with water. The organic layer was dried, filtered, and concentrated. This solid was dissolved in DMF (15 mL) and HMPA (2 mL) prior to the addition of NaSMe (1.1 g) and 18-crown-6 (500 mg). After 18 h, additional HMPA (0.5 mL) was added. After another 3 h, water was added and the solution was extracted with EtOAc. The organic layer was dried, filtered, and concentrated. Flash chromatography of the resulting residue gave (1R,3R,4S)-(4-benzyloxycarbonylamino-3-(methyl)thiomethylcyclohexyl)carbamic acid tert-butyl ester (1.1 g). MS found: (M+H)+=409.2.

Workup

  1. temperatureThis mixture was warmed to RT
  2. customThe CH2Cl2 was removed
  3. additionEtOAc was added along with water
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThis solid was dissolved in DMF (15 mL)
  8. additionHMPA (2 mL) prior to the addition of NaSMe (1.1 g) and 18-crown-6 (500 mg)
  9. waitAfter 18 h
  10. additionadditional HMPA (0.5 mL) was added
  11. waitAfter another 3 h
  12. additionwater was added
  13. extractionthe solution was extracted with EtOAc
  14. customThe organic layer was dried
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-6c82aeb2793d47d194c8882f6a17e65e
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

Loading…