4-Chlorophenyl Isocyanate → HCID 9912033, compound

HRID 602334Notes

Reaction equation

HRID 602334 reaction equation
Cl.[O:2]=[C:3]1[CH2:8][O:7][CH2:6][CH2:5][N:4]1[C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C@H:18]2[CH2:22][C@@H:21]([OH:23])[CH2:20][NH:19]2)=[O:17])=[CH:11][CH:10]=1.C(N(CC)CC)C.[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([N:38]=[C:39]=[O:40])=[CH:34][CH:33]=1>ClCCl>[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39]([N:19]2[CH2:20][C@H:21]([OH:23])[CH2:22][C@@H:18]2[C:16]([NH:15][C:12]2[CH:11]=[CH:10][C:9]([N:4]3[CH2:5][CH2:6][O:7][CH2:8][C:3]3=[O:2])=[CH:14][CH:13]=2)=[O:17])=[O:40])=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 76934-Chlorophenyl IsocyanateHCID 8471TriethylamineHCID 66593341HCID 66593341, compound

Product 1

HCID 9912033HCID 9912033, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

7.3 12.64 g (36.98 mmol) of N-[4-(3-oxomorpholin-4-yl)phenyl]-(2R,4R)-4-hydroxypyrrolidine-2-carboxamide hydrochloride are suspended in 1200 ml of dichloromethane, and 5.4 ml of triethylamine are added with cooling in an ice bath. The solution of 5.96 g (38.83 mmol) of 4-chlorophenyl isocyanate in 100 ml of dichlormethane is subsequently added dropwise to the mixture at 2° C. over the course of 1.5 hours, and the reaction solution is then left to stir for a further 30 minutes with ice cooling. The dichloromethane solution is then washed successively with 100 ml of 1N hydrochloric acid and 100 ml of water and dried over sodium sulfate. After the drying agent has been filtered off and the methylene chloride solution has been evaporated to ⅓ of the original volume in a rotary evaporator, the precipitated product is filtered off, washed with 50 ml of petroleum ether and dried in a desiccator, giving 14.6 g (86%) of 1-N-[(4-chlorophenyl)]-2-N-{[4-(3-oxomorpholin-4-yl)phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide (“A8”) as a white powder, ESI 459; m.p. 216°.

Workup

  1. temperaturewith cooling in an ice bath
  2. waitthe reaction solution is then left
  3. washThe dichloromethane solution is then washed successively with 100 ml of 1N hydrochloric acid and 100 ml of water
  4. dry with materialdried over sodium sulfate
  5. filtrationAfter the drying agent has been filtered off
  6. customthe methylene chloride solution has been evaporated
  7. customto ⅓ of the original volume in a rotary evaporator
  8. filtrationthe precipitated product is filtered off
  9. washwashed with 50 ml of petroleum ether
  10. customdried in a desiccator

Sources & evidence

ORD record
ord-3bc9bf5d723949cc9be649af10df3ef7
Source dataset
uspto-grants-2011_03
Patent number
US07906516B2

Reaction notes

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