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

HRID 986993Notes

Reaction equation

HRID 986993 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. The reaction mixture was partitioned between 4.5 L H2O and 4.5 L IPE. The layers were saparated and the pH of the aqueous layer was adjusted 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), 7.30 (m, 1H).

Workup

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

Sources & evidence

ORD record
ord-1f1cb1dfe6ad49f7937c0f0917f948f5
Source dataset
uspto-grants-2003_10
Patent number
US06630487B2

Reaction notes

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