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

HRID 1852117Notes

Reaction equation

HRID 1852117 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 mmol) was added to a solution of (2S,4R)-methyl 4-hydroxypyrrolidine-2-carboxylate HCl (16.68 g, 92 mmol), (3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoic acid (25 g, 83 mmol) and NEt3 (34.9 mL, 250 mmol) in DCM (250 mL) and stirred at RT for 16 h. The reaction was washed with 1N HCl (3×) and then brine. The organics were dried with magnesium sulfate, filtered and concentrated under vacuum. The crude material was purified via silica gel chromatography using 20-60% Acetone in hexanes to give 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. washThe reaction was washed with 1N HCl (3×)
  2. dry with materialThe organics were dried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe crude material was purified via silica gel chromatography

Sources & evidence

ORD record
ord-0d30d00773d54cafbdb94ecc1123e882
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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