Dichloromethane → (S)-2-(Benzhydrylidene-amino)-3-(3-bromo-4-fluoro-phenyl)-propionic acid tert-butyl ester

HRID 2265307Notes

Reaction equation

HRID 2265307 reaction equation
[C:1]([O:5][C:6](=[O:22])[CH2:7][N:8]=[C:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].C=CCOC(C1C2C(=CC=CC=2)N=CC=1)C1[N+]2(CC3C4C(=CC=CC=4)C=C4C=3C=CC=C4)CC(C=C)C(CC2)C1.[Br-].C(Cl)Cl.[Br:67][C:68]1[CH:69]=[C:70]([CH:73]=[CH:74][C:75]=1[F:76])[CH2:71]Br>CCOCC.O>[C:1]([O:5][C:6](=[O:22])[C@@H:7]([N:8]=[C:9]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH2:71][C:70]1[CH:73]=[CH:74][C:75]([F:76])=[C:68]([Br:67])[CH:69]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 688171N-(Diphenylmethylene)glycine tert-butyl esterHCID 129227103-Bromo-4-fluorobenzyl BromideHCID 223245784-[[1-(Anthracen-9-ylmethyl)-5-ethenyl-1-azoniabicyclo[2.2.2]octan-2-yl]-prop-2-enoxymethyl]quinoline;bromide

Product 1

HCID 86761241(S)-2-(Benzhydrylidene-amino)-3-(3-bromo-4-fluoro-phenyl)-propionic acid tert-butyl esterYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
-55 °C

Procedure

To a flame-dried flask was added (benzhydrylidene-amino)-acetic acid tert-butyl ester (250 mg, 0.846 mmol), O-allyl-N-(9-anthracenylmethyl)-cinchonidinium bromide (51 mg, 0.085 mmol), and DCM (5 mL). The flask was cooled to −55° C. and CsOH.H2O (1.4 g, 8.46 mmol) was added. The mixture was stirred for 30 min, treated with 3-bromo-4-fluorobenzyl bromide (1.1 g, 4.23 mmol), and stirred at −55° C. overnight. The mixture was diluted with Et2O (5 mL) and water (10 mL), warmed to rt, and washed with water and brine. The organic layer was dried (MgSO4) and concentrated. The residue was purified by column chromatography to provide the title compound (300 mg, 74%, er=97:3). MS (ESI+): mass calcd. for C26H25BrFNO2, 482.4; m/z found, 483.4 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.59-7.54 (m, 2H), 7.41-7.20 (m, 7H), 7.02-6.91 (m, 2H), 6.72 (d, J=6.5 Hz, 2H), 4.11-4.07 (m, 1H), 3.19-3.08 (m, 2H), 1.45 (s, 9H).

Workup

  1. stirringstirred at −55° C. overnight
  2. temperaturewarmed to rt
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-d339b6c68792456188fd2781964ea0c5
Source dataset
uspto-grants-2010_12
Patent number
US07855292B2

Reaction notes

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