Ethylmorpholine → HCID 13243450, compound

HRID 1762958Notes

Reaction equation

HRID 1762958 reaction equation
Cl.[CH2:2]([O:9][C:10]1[CH:11]=[CH:12][C:13]([C:22](=[O:36])[CH2:23][N:24]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:25]([CH3:28])([CH3:27])[CH3:26])=[C:14]2[C:18]=1[NH:17][C:16]([C:19]([OH:21])=O)=[CH:15]2)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N1CCOCC1)C.ClC(OCC(C)C)=O.Cl.[CH3:54][O:55][C:56](=[O:59])[CH2:57][NH2:58]>CN(C)C=O.O1CCCC1.C(N(CC)CC)C>[CH3:54][O:55][C:56](=[O:59])[CH2:57][NH:58][C:19]([C:16]1[NH:17][C:18]2[C:14]([CH:15]=1)=[C:13]([C:22](=[O:36])[CH2:23][N:24]([CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:25]([CH3:26])([CH3:27])[CH3:28])[CH:12]=[CH:11][C:10]=2[O:9][CH2:2][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)=[O:21]

Participants

8

Reactant 4

HCID 7525EthylmorpholineHCID 62365Isobutyl chloroformateHCID 122755Glycine methyl ester hydrochlorideHCID 70381215HCID 70381215, compound

Product 1

HCID 13243450HCID 13243450, compoundYield 56.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-10 °C

Procedure

1.00 g of 7-benzyloxy-4-(N-benzyl-N-tert-butylaminoacetyl)-2-indolecarboxylic acid hydrochloride is combined with 4 ml of absolute dimethylformamide and 8 ml of absolute tetrahydrofuran, cooled to -10° C., and combined with 0.52 ml of N-ethylmorpholine and, 5 minutes later, with 0.28 ml of isobutyl chloroformate. The mixture is allowed to stand at -5° C. for 30 minutes, 376 mg of aminoacetic acid methyl ester hydrochloride, 0.39 ml of triethylamine--dissolved in 4 ml of absolute dimethylformamide and 6 ml of absolute tetrahydrofuran--are added thereto, the mixture is stirred for 16 hours at room temperature, concentrated, the residue is taken up in ethyl acetate/water, and the aqueous phase is acidified with 1N hydrochloric acid and once again extracted with ethyl acetate. The combined organic phases are dried, concentrated, and chromatographed over an aluminum oxide column (activity stage II; eluent: methanol/chloroform 1+4), thus obtaining 600 mg of N-[7-benzyloxy-4-(N-benzyl-N-tert-butylaminoacetyl)-2-indolylcarbonyl]aminoacetic acid methyl ester, mp 151.5°-152.5° C. (from methanol/diisopropyl ether).

Workup

  1. concentrationconcentrated
  2. extractiononce again extracted with ethyl acetate
  3. customThe combined organic phases are dried
  4. concentrationconcentrated
  5. customchromatographed over an aluminum oxide column (activity stage II; eluent: methanol/chloroform 1+4)

Sources & evidence

ORD record
ord-9f7ed43c4edd45f59e985b5ea3d395ff
Source dataset
uspto-grants-1989_05
Patent number
US04835175

Reaction notes

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