Diisopropylethylamine → (2S,4R)-methyl 1-((2S,3S)-2-((tert-butoxycarbonyl)amino)-3-(pent-4-en-1-yloxy)pentanoyl)-4-hydroxypyrrolidine-2-carboxylate

HRID 523184Notes

Reaction equation

HRID 523184 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@@H:13]([O:16][CH2:17][CH2:18][CH2:19][CH:20]=[CH2:21])[CH2:14][CH3:15])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[OH:23][C@H:24]1[CH2:28][NH:27][C@H:26]([C:29]([O:31][CH3:32])=[O:30])[CH2:25]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.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]([O:16][CH2:17][CH2:18][CH2:19][CH:20]=[CH2:21])[CH2:14][CH3:15])[C:10]([N:27]1[CH2:28][C@H:24]([OH:23])[CH2:25][C@H:26]1[C:29]([O:31][CH3:32])=[O:30])=[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 90118077(2S,3S)-2-((tert-butoxycarbonyl)amino)-3-(pent-4-en-1-yloxy)pentanoic acid

Product 1

HCID 90121388(2S,4R)-methyl 1-((2S,3S)-2-((tert-butoxycarbonyl)amino)-3-(pent-4-en-1-yloxy)pentanoyl)-4-hydroxypyrrolidine-2-carboxylateYield 107.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round-bottom flask equipped with a stir bar was added (2S,3S)-2-((tert-butoxycarbonyl)amino)-3-(pent-4-en-1-yloxy)pentanoic acid (all material from step 1, 1.00 g, 3.32 mmol), (2S,4R)-methyl 4-hydroxypyrrolidine-2-carboxylate-HCl salt (0.663 g, 3.65 mmol), HATU (1.26 g, 3.32 mmol) and CH2Cl2 (30 mL). To the mixture was added N,N-diisopropylethylamine (1.75 mL, 9.95 mmol). The mixture was stirred at room temperature for 16 h. The mixture was transferred to a separatory funnel and was thrice washed with aq. HCl (1M); then brine. The organic solution was dried over MgSO4; filtered; then concentrated in vacuo to afford (2S,4R)-methyl 1-((2S,3S)-2-((tert-butoxycarbonyl)amino)-3-(pent-4-en-1-yloxy)pentanoyl)-4-hydroxypyrrolidine-2-carboxylate as a yellow oil (1.53 g).

Workup

  1. customTo a round-bottom flask equipped with a stir bar
  2. customThe mixture was transferred to a separatory funnel
  3. washwashed with aq. HCl (1M)
  4. dry with materialThe organic solution was dried over MgSO4
  5. filtrationfiltered
  6. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-aaac23383ec641749ec0b93123ba359c
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Reaction notes

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