Hydrochloric Acid → [1-Benzyl-3-(benzyloxycarbonyl-isobutyl-amino)-2-hydroxy-propyl]-carbamic Acid hexahydro-furo[2,3-b]furan-3-yl Ester

HRID 2224668Notes

Reaction equation

HRID 2224668 reaction equation
[CH2:1]([O:8][C:9](=[O:34])[N:10]([CH2:15][CH:16]([OH:33])[CH:17]([NH:25]C(OC(C)(C)C)=O)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:11][CH:12]([CH3:14])[CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(N(CC)C(C)C)(C)C.[O:45]1[CH:49]2[O:50][CH2:51][CH2:52][CH:48]2[CH:47]([O:53][C:54](=[O:63])ON2C(=O)CCC2=O)[CH2:46]1>O1CCOCC1>[CH2:1]([O:8][C:9](=[O:34])[N:10]([CH2:15][CH:16]([OH:33])[CH:17]([NH:25][C:54]([O:53][CH:47]1[CH:48]2[CH:49]([O:50][CH2:51][CH2:52]2)[O:45][CH2:46]1)=[O:63])[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:11][CH:12]([CH3:13])[CH3:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 17981482Carbonic acid 2,5-dioxo-pyrrolidin-1-yl ester hexahydro-furo[2,3-b]furan-3-yl esterHCID 66769801HCID 66769801, compound

Product 1

HCID 66769651[1-Benzyl-3-(benzyloxycarbonyl-isobutyl-amino)-2-hydroxy-propyl]-carbamic Acid hexahydro-furo[2,3-b]furan-3-yl EsterYield 73.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

(3-tert-Butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-isobutyl-carbamic acid benzyl ester 16 (7.54 g, 15 mmol) and 35 ml of 4M HCl in dioxane were stirred 30 min under an argon atmosphere. The mixture was concentrated in vacuo, and co-evaporated twice with dichloromethane. The residue was dissolved in dichloromethane (50 ml) and N,N-diisopropylethylamine (6.1 ml, 35 mmol), and carbonic acid 2,5-dioxo-pyrrolidin-1-yl ester hexahydro-furo[2,3-b]furan-3-yl ester 17 (4.88 g, 18 mmol) was added. The reaction mixture was stirred overnight, and then concentrated in vacuo. The residue was diluted with dichloromethane, and sequentially washed with brine, 10% KHSO4, brine, saturated NaHCO3, and brine, then dried over MgSO4, and concentrated in vacuo. The oily residue was purified by flash chromatography using 70:30 ethyl acetate hexane as eluant, to give [3-(Hexahydro-furo[2,3-b]furan-3-yloxycarbonylamino)-2-hydroxy-4-phenyl-butyl]-isobutyl-carbamic acid benzyl ester 18 (5.8 g, 73%) as a white solid. TLC: Rf 0.56 (7:3 ethyl acetate:hexane). MS 527 (MH)+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (50 ml)
  3. concentrationconcentrated in vacuo
  4. additionThe residue was diluted with dichloromethane
  5. washsequentially washed with brine, 10% KHSO4, brine, saturated NaHCO3, and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe oily residue was purified by flash chromatography

Sources & evidence

ORD record
ord-310f25b674034757af00127b7b680791
Source dataset
uspto-grants-2008_05
Patent number
US07378441B2

Reaction notes

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