Potassium Carbonate → (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-[(1S,2R)-1-benzyl-3-((cyclopentyloxy)[3-(2-morpholino-2-oxoethoxy)phenyl]sulfonylamino)-2-hydroxypropyl]carbamate

HRID 29194Notes

Reaction equation

HRID 29194 reaction equation
[CH2:1]([C@H:8]([NH:29][C:30](=[O:40])[O:31][C@@H:32]1[C@H:39]2[C@H:35]([O:36][CH2:37][CH2:38]2)[O:34][CH2:33]1)[C@@H:9]([OH:28])[CH:10]([NH:17][S:18]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([OH:27])[CH:22]=1)(=[O:20])=[O:19])OC1CCCC1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:42][C:43]([N:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1)=[O:44].[C:51](=[O:54])([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:1]([C@H:8]([NH:29][C:30](=[O:40])[O:31][C@@H:32]1[C@H:39]2[C@H:35]([O:36][CH2:37][CH2:38]2)[O:34][CH2:33]1)[C@H:9]([OH:28])[CH2:10][N:17]([O:54][CH:51]1[CH2:3][CH2:2][CH2:1][CH2:8]1)[S:18]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH2:42][C:43]([N:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)=[O:44])[CH:22]=1)(=[O:19])=[O:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 139968762-Bromo-1-(morpholin-4-yl)ethan-1-oneHCID 69223281(3R,3aS,6aR)hexahydrofuro [2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(3-hydroxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate

Product 1

HCID 21356316(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-[(1S,2R)-1-benzyl-3-((cyclopentyloxy)[3-(2-morpholino-2-oxoethoxy)phenyl]sulfonylamino)-2-hydroxypropyl]carbamateYield 129.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(3-hydroxyphenyl)sulfonyl]amino-2-hydroxypropyl)carbamate (0.09 mmol, 50 mg) was combined with 2-bromo-1-morpholino-1-ethanone (0.09 mmol, 18 mg) and potassium carbonate (0.26 mmol, 36 mg), and stirred in anhydrous DMF (1 mL) under nitrogen for 15 hours at room temperature. The reaction was concentrated to a residue, dissolved in ethyl acetate, washed in distilled water and brine, and dried over magnesium sulfate. The dried solution was then concentrated and purified by silica gel flash chromatography (1:1 hexanes/ethyl acetate) to provide 41 mg (67%) of a white solid. Rf=0.1 (1:1 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.47 (2H,m), 7.38 (1H,m), 7.32-7.14 (7H,m), 5.64 (1H,s), 5.03(2H,m), 4.91-4.76 (1H,m), 4.78 (2H,s), 3.98-3.89 (2H,m), 3.89-3.77 (2H,m), 3.74-3.63 (8H,m), 3.63-3.52 (2H,m), 3.15 (1H,br.s), 3.08-2.98 (2H,m), 2.98-2.84 (3H,m), 2.84-2.74 (1H,m), 1.89-1.71 (4H,m), 1.71-1.49 (4H,m). MS (ESI): M+H=704.

Workup

  1. concentrationThe reaction was concentrated to a residue
  2. dissolutiondissolved in ethyl acetate
  3. washwashed in distilled water
  4. dry with materialbrine, and dried over magnesium sulfate
  5. concentrationThe dried solution was then concentrated
  6. custompurified by silica gel flash chromatography (1:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-449bb7a6332243be827f8cf40e29a827
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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