Dicyclohexylcarbodiimide → Ammonium Hydroxide

HRID 1937186Notes

Reaction equation

HRID 1937186 reaction equation
[CH3:1][N:2]1C(=[O:7])CC[C@H]1C(O)=O.[C:11]([OH:16])(=[O:15])[C:12]([OH:14])=[O:13].[OH:17][C:18]1[CH:19]=[CH:20][C:21]2[C:25]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([CH2:33][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)=[C:29]([CH3:39])[CH:28]=3)=[C:24]([C:40]3[CH:45]=[CH:44][C:43]([NH:46][C:47]([C@H:49]4[CH2:53][CH2:52][C:51](=[O:54])[NH:50]4)=[O:48])=[CH:42][CH:41]=3)[S:23][C:22]=2[CH:55]=1.ON1C2N=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.C([O-])(O)=O.[Na+]>CN(C=O)C>[NH4+:2].[OH-:7].[C:11]([OH:16])(=[O:15])[C:12]([OH:14])=[O:13].[OH:17][C:18]1[CH:19]=[CH:20][C:21]2[C:25]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([CH2:33][N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)=[C:29]([CH3:39])[CH:28]=3)=[C:24]([C:40]3[CH:45]=[CH:44][C:43]([NH:46][C:47]([CH:49]4[CH2:53][CH2:52][C:51](=[O:54])[N:50]4[CH3:1])=[O:48])=[CH:42][CH:41]=3)[S:23][C:22]=2[CH:55]=1

Participants

8

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 18649403(2S)-1-methyl-5-oxopyrrolidine-2-carboxylic acidHCID 69690662HCID 69690662, compound

Product 2

HCID 14923Ammonium HydroxideHCID 22462748HCID 22462748, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 0° C. solution of N-methylpyroglutamic acid (621 mg; 3.29 mmol; Bull Soc Chim Fr, 1973, (3) (Pt. 2), 1053-6), 3-methyl-4-(1-pyrrolidinylmethyl)phenyl 6-methoxy-2-(4-aminophenyl)benzo[b]thiophen-3-yl ketone (Example 1, Part E; 1.5 g; 3.29 mmol) and 1-hydroxy-7-azabenzotriazole (448 mg; 3.29 mmol) in 50 mL of dry DMF was treated with 1,3-dicyclohexylcarbodiimide (629 mg, 3.29 mmol). The resulting mixture was allowed to gradually warm to ambient temperature. After stirring for 48 h, the reaction mixture was poured into 100 mL of saturated NaHCO3. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with H2O (2×50 mL) and brine (50 mL), dried over K2CO3, filtered and concentrated in vacuo. Radial chromatography (SiO2; gradient of 0.5% to 2% MeOH in CHCl3, saturated with NH4OH) afforded 816 mg (1.4 mmol; 43%) of the title product as a bright yellow foam.

Workup

  1. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  2. washThe combined organic layers were washed with H2O (2×50 mL) and brine (50 mL)
  3. dry with materialdried over K2CO3
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8db2f8d5c578468581c68f7a8eeeaff3
Source dataset
uspto-grants-2002_05
Patent number
US06391901B1

Reaction notes

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