4-Methylmorpholine → HCID 178450149, compound

HRID 1443393Notes

Reaction equation

HRID 1443393 reaction equation
[C:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH:13]([NH:17][C:18]([O:20][CH2:21][CH:22]2[C:34]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:28]3[C:23]2=[CH:24][CH:25]=[CH:26][CH:27]=3)=[O:19])[C:14](O)=[O:15])=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[C:50]1([C:56]2[N:57]=[C:58]([CH:61]3[CH2:70][C:69]4[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=4)[CH2:63][NH:62]3)[NH:59][CH:60]=2)[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>ClCCl>[CH:24]1[C:23]2[CH:22]([CH2:21][O:20][C:18](=[O:19])[NH:17][CH:13]([CH2:12][C:9]3[CH:8]=[CH:7][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[CH:11][CH:10]=3)[C:14](=[O:15])[N:62]3[CH:61]([C:58]4[NH:59][CH:60]=[C:56]([C:50]5[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=5)[N:57]=4)[CH2:70][C:69]4[C:64](=[CH:65][CH:66]=[CH:67][CH:68]=4)[CH2:63]3)[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:28]=2[CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 1001122-(9H-fluoren-9-ylmethoxycarbonylamino)-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoic acidHCID 178420112HCID 178420112, compound

Product 1

HCID 178450149HCID 178450149, compoundYield 88.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

3-(4-tert-Butoxy-phenyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid (1.93 g, 4.2 mmol) was dissolved in dichloromethane (100 mL), cooled to 0° C., then N-methyl-morpholine (0.42 g, 4.2 mmol) was added neat followed by isobutyl chloroformate (0.52 mL, 4 mmol). After 1.25 hour 3-(4-phenyl-1H-imidazol-2-yl)-1,2,3,4-tetrahydro-isoquinoline (1.10 g, 4 mmol) was added neat and the reaction was allowed to warm to room temperature. After 16 hours the reaction was extracted with water, then saturated NaHCO3, dried over Na2SO4, filtered, and concentrated under reduced pressure to give 2.53 g (88%) of brown foam desired product {1-(4-tert-butoxy-benzyl)-2-oxo-2-[3-(4-phenyl-1H-imidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester, which was used without further purification.

Workup

  1. temperatureto warm to room temperature
  2. extractionAfter 16 hours the reaction was extracted with water
  3. dry with materialsaturated NaHCO3, dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-eabf1a83b5464fb9bd847abe923d4350
Source dataset
uspto-grants-2010_02
Patent number
US07659402B2

Reaction notes

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