4-Methylmorpholine → tert-butyl 4-((4-(N-(2-hydroxyethyl)-N-methylcarbamoyl)phenyl)bromomethylene)piperidine-1-carboxylate

HRID 1011280Notes

Reaction equation

HRID 1011280 reaction equation
[CH3:1][N:2]1CC[O:5][CH2:4][CH2:3]1.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18](=[C:21]([Br:31])[C:22]2[CH:27]=[CH:26][C:25]([C:28](O)=[O:29])=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CNCCO>CN(C=O)C.CCOC(C)=O>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18](=[C:21]([Br:31])[C:22]2[CH:27]=[CH:26][C:25]([C:28](=[O:29])[N:2]([CH2:3][CH2:4][OH:5])[CH3:1])=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:9])([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 80162-(Methylamino)ethanolHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 10834544HCID 10834544, compound2×

Product 1

HCID 24897463tert-butyl 4-((4-(N-(2-hydroxyethyl)-N-methylcarbamoyl)phenyl)bromomethylene)piperidine-1-carboxylateYield 772%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-Methylmorpholine (6.7 mL, 60 6 mmol) and 4-[bromo-(4-carboxy-phenyl)-methylene]-piperidine-1-carboxylic acid tert-butyl ester (prepared as for compound 5 in WO2001074806) (20.0 g, 50.5 mmol) in DMF (240 mL) were treated with TBTU (17.8 g, 55.6 mmol) under nitrogen. After stirring for 10 min., 2-(methylamino)ethanol (5.3 mL, 65.7 mmol) was added and the solution stirred for 2 h. The reaction was diluted with EtOAc (350 mL), washed with 2% citric acid, 3% NaHCO3, and brine. The aq. washes were extracted with EtOAc (50 mL). The combined organic phases were dried over Na2SO4 then concentrated in vacuo to a solid. After stirring in hexanes for 5 h, the white solid was collected by filtration and dried under high vacuum to afford 21.0 g (92%) of 1A. 1H NMR (500.333 MHz, CDCl3) δ 7.44 (d, J=8.0 Hz, 2H), 7.32 (d, J=8.0 Hz, 2H), 3.91 (br s, 2H), 3.74 (br s, 2H), 3.54 (t, J=5.8 Hz, 3H), 3.34 (t, J=5.7 Hz, 2H), 3.09 (s, 3H), 3.01 (br s, 1H), 2.64 (t, J=5.9 Hz, 2H), 2.23 (t, J=5.8 Hz, 2H), 1.47 (s, 9H). MS ES+ 453.1.

Workup

  1. stirringthe solution stirred for 2 h
  2. washwashed with 2% citric acid, 3% NaHCO3, and brine
  3. extractionThe aq. washes were extracted with EtOAc (50 mL)
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. concentrationthen concentrated in vacuo to a solid
  6. stirringAfter stirring in hexanes for 5 h
  7. filtrationthe white solid was collected by filtration
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-75482f2bcb8f49bab4b4a0aa539b3912
Source dataset
uspto-grants-2011_07
Patent number
US07977355B2

Reaction notes

Loading…