Morpholine → Benzyl (3S)-3-(4-morpholinylcarbonyl)-3,4-dihydro-2(1H)-isoquinoline carboxylate

HRID 518918Notes

Reaction equation

HRID 518918 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C@H:20]([C:21]([OH:23])=O)[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C(N(CC)CC)C.C(N=C=NCCCN(C)C)C.OC1C2N=NNC=2C=CC=1.[Cl-].[NH4+]>ClCCl>[N:24]1([C:21]([C@@H:20]2[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][N:11]2[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])=[O:23])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1

Participants

8

Reactant 6

HCID 8083MorpholineHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 688307(3S)-2-Carbobenzoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic AcidHCID 178418300HCID 178418300, compound

Product 1

HCID 1118330Benzyl (3S)-3-(4-morpholinylcarbonyl)-3,4-dihydro-2(1H)-isoquinoline carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5 g of (3S)-2-[(benzyloxy)carbonyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid (16 mmol) in 160 mL of dichloromethane there are added 1.5 mL of morpholine (17.6 mmol), then 9 mL of N,N,N-triethylamine (64 mmol), 3.3 g of 1-ethyl-3-(3′-dimethylaminopropyl)-carbodiimide (EDC) (19.2 mmol) and 2.6 g of hydroxybenzotriazole (HOBt) (19.2 mmol). The reaction mixture is stirred at ambient temperature overnight; it is then poured into aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase is then dried over magnesium sulphate, and then filtered and evaporated to dryness. The crude product thereby obtained is then purified by chromatography over silica gel (dichloromethane/methanol gradient). The product is obtained in the form of a foam.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic phase is then dried over magnesium sulphate
  3. filtrationfiltered
  4. customevaporated to dryness

Sources & evidence

ORD record
ord-b22d7901276349759dced9743a3c1059
Source dataset
uspto-grants-2015_08
Patent number
US09115159B2

Reaction notes

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