4-Chlorophenyl Isocyanate → (2R,4R)-4-{[1-(4-Chloro-phenylcarbamoyl)-4-methoxy-pyrrolidine-2-carbonyl]-amino}-benzoic acid methyl ester

HRID 2217588Notes

Reaction equation

HRID 2217588 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([C@H:13]2[CH2:17][C@@H:16]([O:18][CH3:19])[CH2:15][NH:14]2)=[O:12])=[CH:6][CH:5]=1.C(N(CC)C(C)C)(C)C.[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([N:37]=[C:38]=[O:39])=[CH:33][CH:32]=1>C1COCC1>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11]([C@H:13]2[CH2:17][C@@H:16]([O:18][CH3:19])[CH2:15][N:14]2[C:38](=[O:39])[NH:37][C:34]2[CH:35]=[CH:36][C:31]([Cl:30])=[CH:32][CH:33]=2)=[O:12])=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 76934-Chlorophenyl IsocyanateHCID 81531DiisopropylethylamineHCID 68815558(2R,4R)-4-[(4-Methoxy-pyrrolidine-2-carbonyl)-amino]-benzoic acid methyl ester

Product 1

HCID 68807390(2R,4R)-4-{[1-(4-Chloro-phenylcarbamoyl)-4-methoxy-pyrrolidine-2-carbonyl]-amino}-benzoic acid methyl esterYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a solution of 8 (9.19 g, 33.0 mmol) in anhydrous THF (200 mL) at 0° C. was added N,N-diisopropylethylamine (DIEA) (28.7 mL, 165 mmol) and 4-chlorophenyl isocyanate (5.07 g, 33.0 mmol). The solution was stirred at RT overnight before concentrating under reduced pressure. The crude material was purified on a silica gel column eluted with 10% moving to 50% EtOAc in hexanes. Combined and concentrated pure fractions. Remaining EtOAc was azeotroped off with acetonitrile and was lyophilized from acetonitrile/water to give 9 (13.37 g, 94%) as a solid. MS: APCI (AP+): 432.1 (M)+, (AP−): 430.1 (M)−.

Workup

  1. concentrationbefore concentrating under reduced pressure
  2. customThe crude material was purified on a silica gel column
  3. washeluted with 10%
  4. concentrationconcentrated pure fractions
  5. customRemaining EtOAc was azeotroped off with acetonitrile

Sources & evidence

ORD record
ord-6b55ab01d7394030a9d63560b1dbe686
Source dataset
uspto-grants-2008_08
Patent number
US07407974B2

Reaction notes

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