4-Nitrobenzoic Acid → HCID 66593359, compound

HRID 1091261Notes

Reaction equation

HRID 1091261 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[OH:13][C@H:14]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C@@H:16]([C:26](=[O:41])[NH:27][C:28]2[CH:33]=[CH:32][C:31]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][C:35]3=[O:40])=[CH:30][CH:29]=2)[CH2:15]1.[N+:42]([C:45]1[CH:53]=[CH:52][C:48]([C:49](O)=[O:50])=[CH:47][CH:46]=1)([O-:44])=[O:43].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[C:22]([O:21][C:19]([N:17]1[CH2:18][C@@H:14]([O:13][C:49](=[O:50])[C:48]2[CH:47]=[CH:46][C:45]([N+:42]([O-:44])=[O:43])=[CH:53][CH:52]=2)[CH2:15][C@@H:16]1[C:26](=[O:41])[NH:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][C:35]2=[O:40])=[CH:30][CH:29]=1)=[O:20])([CH3:25])([CH3:24])[CH3:23]

Participants

6

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 66593297HCID 66593297, compound

Product 1

HCID 66593359HCID 66593359, compoundYield 211.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

8.1 5.51 ml (35 mmol) of diethyl azodicarboxylate (DEAD) are added dropwise at 0° C. under nitrogen to a solution of 7.0 g (7.26 mmol) of tert-butyl (2R,4R)-4-hydroxy-2-(4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidine-1-carboxylate, 5.77 g (34.5 mmol) of p-nitrobenzoic acid and 9.18 g (35 mmol) of triphenylphosphine in 350 ml of tetrahydrofuran. The reaction mixture is subsequently left to stir at room temperature for 12 hours and evaporated to dryness-under reduced pressure, 20 ml of methylene chloride are added to the residue, and the methylene chloride solution is washed successively with 10 ml of saturated sodium chloride solution and 10 ml of water and dried over sodium sulfate. After the drying agent has been filtered off and the solvent has been stripped off in a rotary evaporator, the residue is triturated with 30 ml of diethyl ether, giving 8.5 g (88.8%) of tert-butyl-(2R,4S)-4-(4-nitrobenzoyloxy)-2-[4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidine-1-carboxylate as slightly yellow crystals, ESI 555. 8.2 Analogously to Example 7, reaction of tert-butyl (2R,4S)-4-(4-nitro-benzoyloxy)-2-[4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidine-1-carboxylate gives the compound (3S,5R)-1-(4-chlorophenylcarbamoyl)-5-[4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidin-3-yl 4-nitrobenzoate as yellowish crystals, ESI 608. 8.3 0.075 ml of 1N sodium hydroxide solution is added with ice cooling to the solution of 50 mg (0.082 mmol) of (3S,5R)-1-(4-chlorophenyl-carbamoyl)-5-[4-(3-oxomorpholin-4-yl)phenylcarbamoyl]pyrrolidin-3-yl 4-nitrobenzoate in 2 ml of methanol, and the reaction mixture is stirred for 15 minutes. The precipitate is filtered off and washed with 2 ml of methanol and dried, giving 35 mg (93%) of 1-N-[(4-chlorophenyl)]-2-N-{[4-(3-oxomorpholin-4-yl)phenyl]}-(2R,4S)-4-hydroxypyrrolidine-1,2-dicarboxamide as colourless crystals, ESI 459, m.p. 243° (decomposition).

Workup

  1. waitThe reaction mixture is subsequently left
  2. customevaporated to dryness-under reduced pressure, 20 ml of methylene chloride
  3. additionare added to the residue
  4. washthe methylene chloride solution is washed successively with 10 ml of saturated sodium chloride solution and 10 ml of water
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter the drying agent has been filtered off
  7. customthe solvent has been stripped off in a rotary evaporator
  8. customthe residue is triturated with 30 ml of diethyl ether

Sources & evidence

ORD record
ord-4bd5c44055c742fca95777f4b8a5fc2b
Source dataset
uspto-grants-2012_03
Patent number
US08129373B2

Reaction notes

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