Methyl iodide → HCID 18454787, compound

HRID 1271612Notes

Reaction equation

HRID 1271612 reaction equation
N1CCC[CH2:2]1.C([Li])CCC.[CH3:11][O:12][CH2:13][CH2:14][NH:15][C:16](=[O:44])[CH2:17][C@H:18]([OH:43])[CH2:19][C@H:20]([OH:42])[CH2:21][CH2:22][C@@H:23]1[C@@H:32]2[C:27](=[CH:28][C@H:29]([CH3:40])[CH2:30][C@@H:31]2[O:33][C:34](=[O:39])[C@@H:35]([CH3:38])[CH2:36][CH3:37])[CH:26]=[CH:25][C@@H:24]1[CH3:41].CI.[Cl-].[NH4+]>CCCCCC.O1CCCC1.O>[CH3:11][O:12][CH2:13][CH2:14][NH:15][C:16](=[O:44])[CH2:17][C@H:18]([OH:43])[CH2:19][C@H:20]([OH:42])[CH2:21][CH2:22][C@@H:23]1[C@@H:32]2[C:27](=[CH:28][C@H:29]([CH3:40])[CH2:30][C@@H:31]2[O:33][C:34](=[O:39])[C:35]([CH3:2])([CH3:38])[CH2:36][CH3:37])[CH:26]=[CH:25][C@@H:24]1[CH3:41]

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 31268PyrrolidineHCID 18454788HCID 18454788, compoundHCID 178418339Butyllithium

Product 1

HCID 18454787HCID 18454787, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
25 °C

Procedure

Tetrahydrofuran (520 ml) and pyrrolidine (90 ml) are mixed and the mixture is cooled to −40° C. n-Butyl lithium in hexane (1.6M, 510 ml) is added under nitrogen atmosphere for 2 hours at −40° C. to −50° C. The contents are stirred for 30 minutes at −35° C. to −40° C. The residue obtained in step 1 is dissolved in tetrahydrofuran (200 ml) and added to the alkali metal amide solution prepared above for 20 minutes at −40° C. to −45° C. The reaction mass is stirred for 1 hour at −40° C. to −45° C. The solution is warmed to −25° C. to −30° C., methyl iodide (29.7 ml) is added for 1 hour at −25° C. to −30° C. and stirred for 30 minutes at −25° C. to −30° C. Saturated ammonium chloride (55 ml) is added to the reaction mass for 10 minutes at −25° C. to −30° C., the solution is then allowed to raise the temperature to 25° C., water (250 ml) is added at 25° C. and stirred for 10 minutes. Then the layers are separated and the organic layer is washed with 100 ml of 2N hydrochloric acid. The organic layer is again washed with water (300 ml), dried on sodium sulfate and concentrated to 150 ml at reduced pressure not allowing the temperature to raise above 50° C. to give N-methoxyethyl-7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-[[2,2-dimethyl-butanoyl]oxy]-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanamide.

Workup

  1. additionis added under nitrogen atmosphere for 2 hours at −40° C. to −50° C
  2. customprepared above for 20 minutes at −40° C. to −45° C
  3. stirringThe reaction mass is stirred for 1 hour at −40° C. to −45° C
  4. temperatureThe solution is warmed to −25° C. to −30° C.
  5. stirringstirred for 30 minutes at −25° C. to −30° C
  6. stirringstirred for 10 minutes
  7. customThen the layers are separated
  8. washthe organic layer is washed with 100 ml of 2N hydrochloric acid
  9. washThe organic layer is again washed with water (300 ml)
  10. customdried on sodium sulfate
  11. concentrationconcentrated to 150 ml at reduced pressure not
  12. temperatureto raise above 50° C.

Sources & evidence

ORD record
ord-a6901eb283124d0183f8d4e20bb8153e
Source dataset
uspto-grants-2007_04
Patent number
US07205415B2

Reaction notes

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