Imidazole → N-benzyl-O-methyl-N2-trityl-D-serinamide

HRID 389385Notes

Reaction equation

HRID 389385 reaction equation
[H-].[Na+].N1C=CN=[CH:4]1.[CH2:8]([NH:15][C:16](=[O:40])[C@@H:17]([CH2:38][OH:39])[NH:18][C:19]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CI>O1CCCC1.O>[CH2:8]([NH:15][C:16](=[O:40])[C@@H:17]([CH2:38][O:39][CH3:4])[NH:18][C:19]([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57734155N-benzyl-N2-trityl-D-serinamide

Product 1

HCID 54752467N-benzyl-O-methyl-N2-trityl-D-serinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-15 °C

Procedure

To a mixture of sodium hydride (6.59 g), imidazole (1.564 g) and tetrahydrofuran (150 ml), a solution of Example 5 product (i.e. N-benzyl-N2-trityl-D-serinamide, 50 g) in tetrahydrofuran (500 ml) was slowly added at −15° C. and the mixture was stirred for 45 minutes at −15° C. Methyl iodide (24.38 g) was slowly added to the mixture for 15 minutes at −15° C. to −5° C. and the formed reaction mixture was stirred at −5° C. for 3 hours. The reaction mixture was cooled to 0° C., water was added to it and then the tetrahydrofuran was recovered completely under vacuum at 40° C. Hexane (250 ml) was added to it and stirred for 15 minutes. The layers were separated and the aqueous layer was neutralized with acetic acid till pH=6.0. Dichloromethane (2×150 ml) was added to the aqueous layer and layers were separated. Oily product was recovered under vacuum at 35° C. to 40° C. from the organic layer. Hexane (100 ml) was added to the oily product and the solution formed was stirred for 15 minutes, filtered and dried to get the titled product of Formula Va.

Workup

  1. customthe formed reaction mixture
  2. stirringwas stirred at −5° C. for 3 hours
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. customthe tetrahydrofuran was recovered completely under vacuum at 40° C
  5. additionHexane (250 ml) was added to it
  6. stirringstirred for 15 minutes
  7. customThe layers were separated
  8. additionDichloromethane (2×150 ml) was added to the aqueous layer and layers
  9. customwere separated
  10. customOily product was recovered under vacuum at 35° C. to 40° C. from the organic layer
  11. additionHexane (100 ml) was added to the oily product
  12. customthe solution formed
  13. stirringwas stirred for 15 minutes
  14. filtrationfiltered
  15. customdried

Sources & evidence

ORD record
ord-a906ecc338324cab83316acb01540327
Source dataset
uspto-grants-2013_02
Patent number
US08378142B2

Reaction notes

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