Triethylamine → (2S,4R)-methyl 1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate

HRID 523169Notes

Reaction equation

HRID 523169 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.[OH:26][C@H:27]1[CH2:31][NH:30][C@H:29]([C:32]([O:34][CH3:35])=[O:33])[CH2:28]1.[C:36]([O:40][C:41]([NH:43][CH:44]([C@H:48]([CH3:56])[CH2:49][CH:50]([CH3:55])[CH2:51][CH2:52][CH:53]=[CH2:54])[C:45](O)=[O:46])=[O:42])([CH3:39])([CH3:38])[CH3:37].CCN(CC)CC>C(Cl)Cl>[C:36]([O:40][C:41]([NH:43][C@@H:44]([C@H:48]([CH3:56])[CH2:49][CH:50]([CH3:55])[CH2:51][CH2:52][CH:53]=[CH2:54])[C:45]([N:30]1[CH2:31][C@H:27]([OH:26])[CH2:28][C@H:29]1[C:32]([O:34][CH3:35])=[O:33])=[O:46])=[O:42])([CH3:39])([CH3:38])[CH3:37]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 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 86683236(3R)-2-(tert-butoxycarbonylamino)-3,5-dimethylnon-8-enoic acid

Product 1

HCID 86683197(2S,4R)-methyl 1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylateYield 30.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (“HATU”, 31.7 g, 83.0 mmol) was added to a solution of (2S,4R)-methyl 4-hydroxypyrrolidine-2-carboxylate HCl salt (16.7 g, 92.0 mmol), (3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoic acid (25 g, 83 mmol) and NEt3 (35 mL, 250 mmol) in CH2Cl2 (250 mL) and the solution was stirred at room temperature for 16 h. The reaction solution was transferred to a reparatory funnel and was washed with aqueous 1N HCl (3×) and then brine. The organics were dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified via silica gel chromatography (hexane:acetone 80:20 to 40:60) to afford the desired product (2S,4R)-methyl 1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (10.8 g, 30% yield), MS: MS m/z 427.2 (M++1) and the undesired product (2S,4R)-methyl 1-((2R,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (12 g, 34% yield), MS: MS m/z 427.2 (M++1).

Workup

  1. customThe reaction solution was transferred to a reparatory funnel
  2. washwas washed with aqueous 1N HCl (3×)
  3. dry with materialThe organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified via silica gel chromatography (hexane:acetone 80:20 to 40:60)

Sources & evidence

ORD record
ord-237777a871544644b20b715a3ab97c6f
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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