N-Methylcyclohexylamine → HCID 66891527, compound

HRID 2361900Notes

Reaction equation

HRID 2361900 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]=[CH:18][CH2:19]O)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:21][CH2:22][N:23]([CH2:26][CH3:27])[CH2:24][CH3:25].CS(Cl)(=O)=[O:30].[CH:33]1([NH:39][CH3:40])[CH2:38][CH2:37]CCC1.[C:41]([O-])(O)=[O:42].[Na+]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]=[CH:18][CH2:19][N:23]3[CH2:24][CH2:25][O:30][CH2:21][CH2:22]3)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3].[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH:37]=[CH:38][CH2:33][N:39]3[CH2:40][CH2:41][O:42][CH2:26][CH2:27]3)[CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 7514N-MethylcyclohexylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 668912231,1-Dimethylethyl 5-(3-hydroxy-1-propen-1-yl)-1H-indole-1-carboxylate

Product 2

HCID 66891527HCID 66891527, compoundHCID 66892132HCID 66892132, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution 5-(3-hydroxy-propenyl)-indole-1-carboxylic acid tert-butyl ester (0.95 mg, 3.48 mmol, 1.0 eq.) and Et3N (1.8 mL, 3.0 eq.) in methylene chloride (10 mL) at 0° C. was added MsCl (0.40 mL, 1.5 eq.). The resulting mixture was stirred for 30 min and wormed to room temperature and stirred for additional 1 h. Then cyclohexyl-methyl-amine (8.3 mL, 18 eq.) was introduced and the resulting mixture was stirred over weekend, diluted with sat. NaHCO3 and the separated aqueous phase was extracted with 3×EtOAc. The combined organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography (50% EtOAc/hexanes) to give 5-(3-morpholin-4-yl-propenyl)-indole-1-carboxylic acid tert-butyl ester or similarly 6-(3-morpholin-4-yl-propenyl)-indole-1-carboxylic acid tert-butyl ester.

Workup

  1. customwormed to room temperature
  2. stirringstirred for additional 1 h
  3. stirringthe resulting mixture was stirred over weekend
  4. extractionthe separated aqueous phase was extracted with 3×EtOAc
  5. dry with materialThe combined organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-151477b758db49d786bebb9b27820bd8
Source dataset
uspto-grants-2014_04
Patent number
US08691814B2

Reaction notes

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