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

HRID 1067206Notes

Reaction equation

HRID 1067206 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 9, 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 vacua 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) δ1.44 (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 vacua
  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-501db7101d8f40dd8fa3e4739b11e789
Source dataset
uspto-grants-2001_06
Patent number
US06248717B1

Reaction notes

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