1-(Bromomethyl)-2,4-difluorobenzene → HCID 22557094, compound

HRID 1358695Notes

Reaction equation

HRID 1358695 reaction equation
[C:1]([NH:8][C@@H:9]([C:12]([OH:14])=[O:13])[CH2:10][OH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC(C)([O-])C.[K+].[F:21][C:22]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:23]=1[CH2:24]Br>C1COCC1.CN(C=O)C>[C:4]([O:3][C:1]([NH:8][CH:9]([CH2:10][O:11][CH2:24][C:23]1[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:22]=1[F:21])[C:12]([OH:14])=[O:13])=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 3

HCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 637603(R)-2-tert-butoxycarbonylamino-3-hydroxy propionic acidHCID 23665647Potassium tert-butoxide

Product 1

HCID 22557094HCID 22557094, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-Boc-(D)-serine (452 g, 2.2026 mol) in a mixture of THF (7 L) and DMF (3 L) at about 0° C. was added potassium tert-butoxide solution (515.8 g, 4.5963 mol). The reaction mixture was stirred at about 0° C. for about 30 min., then 2,4-difluorobenzyl bromide (456.5 g, 2.2051 mol) was added. After warming to room temperature, the reaction mixture was concentrated in vacuo to remove the THF. Partitioned the reaction mixture between 4.5 L H2O and 4.5 L IPE. Separated the layers and adjusted the pH of the aqueous layer with 1 N HCl to about 3. The aqueous layer was extracted twice with 4 L each of IPE. The organic solution was dried over Na2SO4, and concentrated in vacuo to yield a yellow waxy solid (518.0 g, yield: 70.9%). 1H-NMR (CDCl3) δ 1.44 (s, 9H), 3.73 (m, 1H), 3.94 (d, 1H), 4.44 (br s, 1H), 4.54 (s, 2H), 5.34 (m, 1H), 6.78 (m, 1H), 6.84 (m, 1H), 730 (m, 1H).

Workup

  1. temperatureAfter warming to room temperature
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customto remove the THF
  4. customPartitioned the reaction mixture between 4.5 L H2O and 4.5 L IPE
  5. customSeparated the layers
  6. extractionThe aqueous layer was extracted twice with 4 L each of IPE
  7. dry with materialThe organic solution was dried over Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-64c535d5f2ed44df9046e7ce9be27365
Source dataset
uspto-grants-2003_07
Patent number
US06596867B2

Reaction notes

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