4-Methylmorpholine → HCID 178501437, compound

HRID 526813Notes

Reaction equation

HRID 526813 reaction equation
[C:1]([O:5][C:6]([N:8]=[C:9]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[NH:10][CH2:11][CH2:12][CH2:13][CH2:14][C@@H:15]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:16](O)=[O:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:35][CH2:36][CH2:37][CH2:38][CH2:39][C@@H:40]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C:41]([O:43][CH3:44])=[O:42].CN1CCOCC1.CCOC1N(C(OCC)=O)C2C(=CC=CC=2)C=C1>C(Cl)Cl.O>[C:31]([O:30][C:28]([NH:27][C:9]([NH:10][CH2:11][CH2:12][CH2:13][CH2:14][C@@H:15]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:16](=[O:17])[NH:35][CH2:36][CH2:37][CH2:38][CH2:39][C@@H:40]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C:41]([O:43][CH3:44])=[O:42])=[N:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:29])([CH3:32])([CH3:33])[CH3:34]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 29926888(R)-Methyl 6-amino-2-((tert-butoxycarbonyl)amino)hexanoateHCID 178454264HCID 178454264, compound

Product 1

HCID 178501437HCID 178501437, compoundYield 73.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred solution of acid 8 (1.95 g, 4.00 mmol) and amine 14 (1.04 g, 4.00 mmol) in CH2Cl2 (60 mL) was charged with NMM (2.64 mL, 24.0 mmol) and EEDQ (1.97 g, 8.00 mmol). The resulting mixture was stirred at room temperature for 16 h. Water (20 mL) was added to the reaction mixture and extracted with CH2Cl2 (3×50 mL). The combined organic extract was washed with brine and dried over Na2SO4. The solvent was removed and the residue was purified by column chromatography (silica gel, 20% to 40% EtOAc in hexanes) to afford amide 15 (2.15 g, 73% over two steps) as a white solid: 1H NMR (400 MHz, CD3OD) δ 4.10-4.02 (m, 1H), 4.01-3.92 (m, 1H), 3.70 (s, 3H), 3.35 (t, J=6.8 Hz, 2H), 3.24-3.10 (m, 2H), 1.83-1.67 (m, 2H), 1.66-1.55 (m, 4H), 1.52 (s, 9H), 1.46 (s, 9H), 1.45-1.35 (m, 6H), 1.438 (s, 9H), 1.431 (s, 9H).

Workup

  1. extractionextracted with CH2Cl2 (3×50 mL)
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed
  6. customthe residue was purified by column chromatography (silica gel, 20% to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8158aeebfe334fb8877065ad6739d124
Source dataset
uspto-grants-2016_05
Patent number
US09346753B2

Reaction notes

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