(2S,4R)-tert-butyl 4-(benzyloxycarbonylamino)-2-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidine-1-carboxylate → benzyl (3R,5S)-5-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidin-3-ylcarbamate

HRID 1630081Notes

Reaction equation

HRID 1630081 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][N:15](C(OC(C)(C)C)=O)[C@H:14]([C:24](=[O:40])[NH:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)=[CH:28][CH:27]=2)[CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>Cl>[F:39][C:36]1[CH:35]=[CH:34][C:33]([O:32][C:29]2[CH:30]=[CH:31][C:26]([NH:25][C:24]([C@H:14]3[NH:15][CH2:16][C@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH2:13]3)=[O:40])=[CH:27][CH:28]=2)=[CH:38][CH:37]=1

Participants

3

Reactant 1

HCID 67009501(2S,4R)-tert-butyl 4-(benzyloxycarbonylamino)-2-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidine-1-carboxylate

Product 1

HCID 68201126benzyl (3R,5S)-5-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidin-3-ylcarbamateYield 30%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

Step (c) A flask was charged with (2S,4R)-tert-butyl 4-(benzyloxycarbonylamino)-2-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidine-1-carboxylate and hydrogen chloride (4N in dioxane, 20 mL). The reaction mixture was stirred at ambient temperature for 1 hour and then quenched with saturated sodium bicarbonate (aq., 100 mL). The mixture was extracted with ethyl acetate (30 mL) and the extract was washed with deionized water (30 mL) and then brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was triturated with ethyl acetate to provide benzyl (3R,5S)-5-(4-(4-fluorophenoxy)phenylcarbamoyl)pyrrolidin-3-ylcarbamate (1.20 g, 2.67 mmol, 30% yield over 4 steps) as an off-white solid.

Workup

  1. customquenched with saturated sodium bicarbonate (aq., 100 mL)
  2. extractionThe mixture was extracted with ethyl acetate (30 mL)
  3. washthe extract was washed with deionized water (30 mL)
  4. dry with materialbrine (30 mL), dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was triturated with ethyl acetate

Sources & evidence

ORD record
ord-4dde0d1d5b08449b876aa16c03447d8e
Source dataset
uspto-grants-2014_07
Patent number
US08791102B2

Reaction notes

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