Ethyl Acetate → 3(S)-(6-chloro-9H-beta-carbolin-8-ylcarbamoyl)-morpholine-4-carboxylic acid tert-butyl ester

HRID 12207

Reaction equation

HRID 12207 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[CH:19]=[C:20]2[C:28](=[C:29]([NH2:31])[CH:30]=1)[NH:27][C:26]1[CH:25]=[N:24][CH:23]=[CH:22][C:21]2=1.CCN=C=NCCCN(C)C.CCOC(C)=O>N1C=CC=CC=1.O.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][C@H:9]1[C:14](=[O:16])[NH:31][C:29]1[CH:30]=[C:18]([Cl:17])[CH:19]=[C:20]2[C:28]=1[NH:27][C:26]1[CH:25]=[N:24][CH:23]=[CH:22][C:21]2=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 1512537(3S)-4-(tert-Butoxycarbonyl)morpholine-3-carboxylic acidHCID 213627016-Chloro-9H-beta-carbolin-8-amine

Product 1

HCID 671669503(S)-(6-chloro-9H-beta-carbolin-8-ylcarbamoyl)-morpholine-4-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1049PyridineSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of morpholine-3(S),4-dicarboxylic acid 4-tert-butyl ester (2.83 g, 12.7 mmol) in pyridine (106 ml) was stirred at RT. 6-chloro-9H-β-carbolin-8-ylamine (2.30 g, 10.6 mmol) was added, followed by EDCI (4.06 g, 21.2 mmol). The clear orange-to-brown solution was stirred at RT for 14 hr. The solution was diluted with H2O (120 ml) and poured into a separatory funnel containing EtOAc (200 ml), H2O (100 ml) and brine (100 ml). The mixture was shaken and the layers were separated. The aqueous layer was extracted with EtOAc (2×50 ml) and the combined organic layers were washed with brine. The organic layer was dried, filtered and concentrated to a reduced volume, then added drop-wise to a stirring solution of 1:1 Et2O/hexanes (500 ml). The precipitate which formed was filtered and washed with 1:1 Et2O/Hexanes. The filtrate was concentrated to a reduced volume and a second crop of precipitate was collected. The solid product was placed under high vacuum for 2 hr to yield 3(S)-(6-chloro-9H-β-carbolin-8-ylcarbamoyl)-morpholine-4-carboxylic acid tert-butyl ester as a pale yellow to pale brown solid (4.36 g).

Workup

  1. additionpoured into a separatory funnel
  2. stirringThe mixture was shaken
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc (2×50 ml)
  5. washthe combined organic layers were washed with brine
  6. customThe organic layer was dried
  7. filtrationfiltered
  8. concentrationconcentrated to a reduced volume
  9. additionadded drop-wise to a stirring solution of 1:1 Et2O/hexanes (500 ml)
  10. customThe precipitate which formed
  11. filtrationwas filtered
  12. washwashed with 1:1 Et2O/Hexanes
  13. concentrationThe filtrate was concentrated to a reduced volume
  14. customa second crop of precipitate was collected
  15. waitThe solid product was placed under high vacuum for 2 hr

Sources & evidence

ORD record
ord-2b280253fe694eeb9c97b4f613f7983b
Source dataset
uspto-grants-2010_06
Patent number
US07727985B2

Linked notes

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