Hydrochloric Acid → 2-tert-Butoxycarbonylamino-3-(3,5-dichlorobenzyloxy)-propionic acid

HRID 1060569Notes

Reaction equation

HRID 1060569 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:12]([OH:14])=[O:13])[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Cl:17][C:18]1[CH:23]=[C:22]([CH2:24]Cl)[CH:21]=[C:20]([Cl:26])[CH:19]=1.Cl>CN(C)C=O.C(OCC)C>[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:10][O:11][CH2:24][C:22]1[CH:23]=[C:18]([Cl:17])[CH:19]=[C:20]([Cl:26])[CH:21]=1)[C:12]([OH:14])=[O:13])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 1378803,5-Dichlorobenzyl chlorideHCID 637603(R)-2-tert-butoxycarbonylamino-3-hydroxy propionic acid

Product 1

HCID 222934132-tert-Butoxycarbonylamino-3-(3,5-dichlorobenzyloxy)-propionic acid

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-t-butoxycarbonyl-D-serine (10.0 g, 48.7 mol) in N,N-dimethylformamide (150 mL) at about 0 ° C. was added sodium hydride (4.0 g, 60% dispersion in mineral oil, 99.84 mmol) portionwise. The mixture was stirred for about 30 minutes, and then a solution of 1,3-dichloro-5-chloromethyl-benzene (9.5 mL, 48.7 mmol) in ethyl ether (40 mL) was added. The reaction was allowed to slowly warm to room temperature overnight. The reaction was then quenched with 1N NaOH, the mixture extracted three times with dichloromethane. The combined organic layers were then washed three times with water, 1N HCl, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give crude product. The original basic aqueous layer was then acidified to about pH 4 with 1N HCl, and the mixture was extracted three times with dichloromethane. These three organic layers were combined and washed three times each with water and brine then dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give an additional 620 mg of crude product. Both product fractions were combined and purified by silica gel chromatography using 5% methanol/chloroform as eluent and yielded the title compound of part 1-E (12.39 g, 70%): −APcl MS (M−1)− 363, (M−3)− 361; 1H NMR=400 MHz (CDCl3) 67 : 7.13 (arom, s, 3H), 5.42 (NH, d, 1H), 4.50 (CHCO2H, m, 1H), 4.45 (PhCH2O, s, 2H), 3.82 (CH2OBz, d of d, 2H), 1.43 (BOC, s, 9H).

Workup

  1. customThe reaction was then quenched with 1N NaOH
  2. extractionthe mixture extracted three times with dichloromethane
  3. washThe combined organic layers were then washed three times with water, 1N HCl
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give crude product
  8. extractionthe mixture was extracted three times with dichloromethane
  9. washwashed three times each with water and brine
  10. dry with materialthen dried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto give an additional 620 mg of crude product
  14. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-b5c0433f03334c2582504472b26fa684
Source dataset
uspto-grants-2003_02
Patent number
US06525047B2

Reaction notes

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