Triethylamine → HCID 57200321, compound

HRID 2289051Notes

Reaction equation

HRID 2289051 reaction equation
[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][S:8][C@@H:9]2[CH2:13][N:12]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=3)=[O:15])[C@H:11]([C:27](O)=[O:28])[CH2:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.C(Cl)(=O)OCC.[BH4-].[Na+]>O1CCCC1.O.C(OCC)(=O)C>[OH:28][CH2:27][C@@H:11]1[CH2:10][C@H:9]([S:8][CH2:7][C:6]2[CH:30]=[CH:31][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH2:13][N:12]1[C:14]([O:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]([N+:24]([O-:26])=[O:25])=[CH:22][CH:23]=1)=[O:15]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-proline

Product 1

HCID 57200321HCID 57200321, compoundYield 44.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-12.5 °C

Procedure

(2S,4S)-4-(4-Methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid (10 g) and triethylamine (3.59 ml) were dissolved in tetrahydrofuran (25 ml), followed by stirring at -15 to -10° C. To the mixture, ethyl chlorocarbonate (2.46 ml) was added at the same temperature, followed by stirring at the same temperature for 15 minutes and then at 0-5° C. for one hour. The reaction mixture was filtered through Celite and the residue was washed with tetrahydrofuran (15 ml). The tetrahydrofuran solution was cooled to 0-5° C., followed by the addition of a solution, which had been obtained by dissolving sodium borohydride (1.9 g) in water (20 ml), in three portions below 25° C. The resulting mixture was stirred at room temperature for one hour. Ethyl acetate (100 ml) was added to the reaction mixture. The resulting mixture was washed successively with water, 1N hydrochloric acid, a saturated aqueous solution of sodium bicarbonate and saline; and then dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was subjected to chromatography through a silica gel column. From the fractions eluted with a 1:1 solvent mixture of ethyl acetate and cyclohexane, (2S,4S)-2-hydroxymethyl-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (4.3 g) was obtained.

Workup

  1. stirringby stirring at the same temperature for 15 minutes
  2. filtrationThe reaction mixture was filtered through Celite
  3. washthe residue was washed with tetrahydrofuran (15 ml)
  4. temperatureThe tetrahydrofuran solution was cooled to 0-5° C.
  5. additionfollowed by the addition of a solution, which
  6. customhad been obtained
  7. customin three portions below 25° C
  8. stirringThe resulting mixture was stirred at room temperature for one hour
  9. washThe resulting mixture was washed successively with water, 1N hydrochloric acid
  10. dry with materialand then dried over anhydrous sodium sulfate
  11. distillationThe solvent was distilled off
  12. washFrom the fractions eluted with a 1:1 solvent mixture of ethyl acetate and cyclohexane

Sources & evidence

ORD record
ord-f43ed50bb6c94c0992b7b9d2d9878ba8
Source dataset
uspto-grants-2000_07
Patent number
US06090802

Reaction notes

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