Diisopropylethylamine → (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl 3-[(1,3-benzodioxol-5-ylsulfonyl)(tetrahydro-2H-pyran-4-yloxy)amino]-1-benzyl-2-hydroxypropylcarbamate

HRID 29198

Reaction equation

HRID 29198 reaction equation
[CH2:1]([C@H:8]([NH:20][C:21](=[O:31])[O:22][C@@H:23]1[C@H:30]2[C@H:26]([O:27][CH2:28][CH2:29]2)[O:25][CH2:24]1)[C@H:9]([OH:19])[CH2:10][NH:11][O:12][CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:32]1[C:36]2[CH:37]=[CH:38][C:39]([S:41](Cl)(=[O:43])=[O:42])=[CH:40][C:35]=2[O:34][CH2:33]1.C(N(C(C)C)CC)(C)C>C1COCC1.C(OCC)(=O)C>[O:32]1[C:36]2[CH:37]=[CH:38][C:39]([S:41]([N:11]([O:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH2:10][CH:9]([OH:19])[CH:8]([NH:20][C:21](=[O:31])[O:22][C@@H:23]3[C@H:30]4[C@H:26]([O:27][CH2:28][CH2:29]4)[O:25][CH2:24]3)[CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)(=[O:42])=[O:43])=[CH:40][C:35]=2[O:34][CH2:33]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 49134011,3-Benzodioxole-5-sulfonyl chlorideHCID 58683433(3R, 3aS, 6aR)hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-1-benzyl-2-hydroxy-3-[(tetrahydro-2H-pyran-4-yloxy)amino]propylcarbamate

Product 1

HCID 21356268(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl 3-[(1,3-benzodioxol-5-ylsulfonyl)(tetrahydro-2H-pyran-4-yloxy)amino]-1-benzyl-2-hydroxypropylcarbamateYield 39%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-2-hydroxy-3-[(tetrahydro-2H-pyran-4-yloxy)amino]propylcarbamate (0.23 mmol, 100 mg) was combined 1,3-benzodioxole-5-sulfonyl chloride (0.28 mmol, 61 mg), diisopropylethylamine (0.69 mmol, 0.12 mL) in anhydrous THF (2 mL) and allowed to stir 72 hours at room temperature under nitrogen. The reaction was diluted with ethyl acetate and washed with 1N HCl, saturated sodium bicarbonate solution, brine and was dried over magnesium sulfate. The solution was concentrated under vacuum and the crude product was purified by silica gel chromatography (1:5 hexanes/ethyl acetate). The purified oil was crystallized to provide 55 mg (39%) of white crystals. Rf=0.2 (1:5 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.38-7.13 (9H,m), 6.90 (1H,d), 6.10 (2H,s), 5.64 (1H,s), 5.02 (1H,m), 4.82 (1H,m), 4.41 (1H,m), 3.99-3.79 (6H,m), 3.72-3.59 (2H,m), 3.49-3.33 (2H,m), 3.25-2.51 (6H,m), 2.09-1.98 (2H,m), 1.69-1.43 (2H,m). MS (ESI): M+H=621.

Workup

  1. washwashed with 1N HCl, saturated sodium bicarbonate solution, brine
  2. dry with materialwas dried over magnesium sulfate
  3. concentrationThe solution was concentrated under vacuum
  4. customthe crude product was purified by silica gel chromatography (1:5 hexanes/ethyl acetate)
  5. customThe purified oil was crystallized

Sources & evidence

ORD record
ord-feb4dfa789cb4d71bb2810c500b19571
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Linked notes

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