Hydrochloric Acid → HCID 13882365, compound

HRID 979653Notes

Reaction equation

HRID 979653 reaction equation
[CH3:1][O:2][C:3](=[O:22])[C@H:4]([OH:21])[C@@H:5]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[H-].[Na+].Cl.C(OCC1C=CC=CC=1)C1C=CC=CC=1>CN(C)C=O.CCOCC>[CH3:1][O:2][C:3](=[O:22])[C@H:4]([O:21][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C@@H:5]([NH:13][C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 7657Dibenzyl etherHCID 24758Sodium hydrideHCID 11809228HCID 11809228, compound

Product 1

HCID 13882365HCID 13882365, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(S)-3-t-butoxycarbonylamino-(R)-2-hydroxy-4-cyclohexylbutyric acid methyl ester (4.58 g., 14.52 mmol) was dissolved in anhydrous dimethylformamide (30 ml.) together with benzyl bromide (2.6 ml., 21.7 mmol) and cooled to 0° C. Sodium hydride (freed of oil by washing with hexane, 450 mg., 19.6 mmol) was added in one portion and the mixture was stirred under nitrogen and allowed to warm to 25° C. over a period of about 15 minutes. The mixture was poured slowly into a stirred ice-cooled mixture of ether (500 ml.) and excess aqueous 1N hydrochloric acid, and was then combined with two previous reaction mixtures where a total of 4.27 mmol (1.34 g.) of this hydroxy methyl ester had been etherified and worked up in an identical fashion. The ether layer was separated and the aqueous layer was extracted thoroughly with ether. The ether layers were combined and washed with 1M lithium chloride solution (2×30 ml.), and dried over magnesium sulfate. The concentrate was chromatographed on silica (0.032-0.064 mm) in 1:6 ether-hexane. Several impure fractions were combined, concentrated, and rechromatographed on 50 g. silica, eluting with 1:10 ether-hexane. The pure fractions combined and concentrated gave 6.45 g. (85%) of the benzyl ether.

Workup

  1. temperatureto warm to 25° C. over a period of about 15 minutes
  2. temperaturecooled
  3. customThe ether layer was separated
  4. extractionthe aqueous layer was extracted thoroughly with ether
  5. washwashed with 1M lithium chloride solution (2×30 ml.)
  6. dry with materialdried over magnesium sulfate
  7. customThe concentrate was chromatographed on silica (0.032-0.064 mm) in 1:6 ether-hexane
  8. concentrationconcentrated
  9. customrechromatographed on 50 g
  10. washsilica, eluting with 1:10 ether-hexane
  11. concentrationconcentrated
  12. customgave 6.45 g

Sources & evidence

ORD record
ord-2cd4af35343f41c3962eb7f60bfe0b91
Source dataset
uspto-grants-1987_05
Patent number
US04668769

Reaction notes

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