Diisopropylethylamine → HCID 86685806, compound

HRID 2361591Notes

Reaction equation

HRID 2361591 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C@H:13]([CH3:21])[CH2:14][CH2:15][CH2:16][CH:17]([CH3:20])[CH:18]=[CH2:19])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:22][O:23][C:24]([C@H:26]1[NH:30][CH2:29][C@H:28]([OH:31])[CH2:27]1)=[O:25].Cl.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:13]([CH3:21])[CH2:14][CH2:15][CH2:16][CH:17]([CH3:20])[CH:18]=[CH2:19])[C:10]([N:30]1[CH2:29][C@H:28]([OH:31])[CH2:27][C@H:26]1[C:24]([O:23][CH3:22])=[O:25])=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114353194-Hydroxy-L-proline methyl ester hydrochlorideHCID 86685804HCID 86685804, compound

Product 1

HCID 86685806HCID 86685806, compoundYield 46.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a slurry of (3R)-2-((tert-butoxycarbonyl)amino)-3,7-dimethylnon-8-enoic acid (6.5 g, 21.7 mmol), L-4-hydroxyproline methyl ester hydrochloride (3.9 g, 21.7 mmol) and O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (8.36 g, 21.7 mmol) in DCM (50 mL) at 0° C., N,N-diisopropylethylamine (11.5 mL, 66.6 mmol) was added dropwise. The resulting light yellow mixture was stirred at rt overnight, washed with 1M HCl (35 ml) and brine, dried over Na2SO4, filtered, concentrated in vacuo. The residual oil (12 g) was purified by conventional column chromatography (60-120 g silica gel column), eluted with 4%˜8% IPA-Hexane to afford the desired product (2S,4R)-methyl 1-((2S,3R)-2-(tert-butoxycarbonylamino)-3,7-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (9a, 4.3 g, 46% yield) as a white foam and the undesired diastereomer (2S,4R)-methyl 1-((2R,3R)-2-(tert-butoxycarbonylamino)-3,7-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (9b, 1.9 g, 20% yield) as a viscous oil. 1H NMR (400 MHz, CDCl3): δ ppm 5.73-5.64 (m, 1H), 5.19-5.17 (m, 1H), 4.97-4.88 (m, 2H), 4.70-4.66 (t, J=8.4 Hz, 1H), 4.53 (bs, 1H), 4.29-4.25 (m, 1H), 3.99-3.96 (d, J=10.8 Hz, 3H), 3.72 (s, 3H), 3.70-3.66 (m, 1H), 2.34-2.11 (m, 1H), 2.10-2.00 (m, 2H), 1.85-1.81 (m, 1H), 1.49-1.41 (m, 9H), 1.39-1.14 (m, 3H), 0.98-0.86 (m, 7H) MS: MS m/z 427.2 (M++1).

Workup

  1. washwashed with 1M HCl (35 ml) and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residual oil (12 g) was purified by conventional column chromatography (60-120 g silica gel column)
  6. washeluted with 4%˜8% IPA-Hexane

Sources & evidence

ORD record
ord-e4dfd9c0883b4895a925bca725a799b6
Source dataset
uspto-grants-2014_04
Patent number
US08691757B2

Reaction notes

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