Diisopropylethylamine → 4-(4-Bromo-benzenesulfonyloxy)-1-[2-tert-butoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidine-2-carboxylic acid methyl ester

HRID 1893682Notes

Reaction equation

HRID 1893682 reaction equation
Cl.[CH3:2][O:3][C:4]([CH:6]1[CH2:10][CH:9]([O:11][S:12]([C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=2)(=[O:14])=[O:13])[CH2:8][NH:7]1)=[O:5].[C:22]([O:26][C:27]([NH:29][CH:30]([CH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1)[C:31](O)=[O:32])=[O:28])([CH3:25])([CH3:24])[CH3:23].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:2][O:3][C:4]([CH:6]1[CH2:10][CH:9]([O:11][S:12]([C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=2)(=[O:14])=[O:13])[CH2:8][N:7]1[C:31](=[O:32])[CH:30]([NH:29][C:27]([O:26][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:28])[CH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1)=[O:5]

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 223091982-(((Tert-butoxy)carbonyl)amino)-2-(oxan-4-yl)acetic acidHCID 87516774L-Proline, 4-[[(4-bromophenyl)sulfonyl]oxy]-, methyl ester, hydrochloride (1:1), (4S)-

Product 1

HCID 766050644-(4-Bromo-benzenesulfonyloxy)-1-[2-tert-butoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidine-2-carboxylic acid methyl esterYield 70.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(4-bromo-benzenesulfonyloxy)-pyrrolidine-2-carboxylic acid methyl ester HCl salt (4 g, 10 mmol) in DCM (50 mL) was added tert-butoxycarbonylamino-(tetrahydro-pyran-4-yl)-acetic acid (2.86 g, 11 mmol), HATU (5.7 g, 15 mmol) and DIPEA (7 mL, 40 mmol). The solution was stirred at room temperature for 16 h. The solution was diluted with DCM and washed twice with aq NH4Cl and brine. The organic layer was dried over MgSO4 and concentrated in vacuo. The desired product was purified by silica gel column chromatography from hexane/EtOAc to provide 4-(4-bromo-benzenesulfonyloxy)-1-[2-tert-butoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidine-2-carboxylic acid methyl ester (4.25 g 70% yield). LCMS found 606 ([M+H]+.

Workup

  1. washwashed twice with aq NH4Cl and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe desired product was purified by silica gel column chromatography from hexane/EtOAc

Sources & evidence

ORD record
ord-87b99586f6c24e27a8219a74a4d89c75
Source dataset
uspto-grants-2013_08
Patent number
US08513186B2

Reaction notes

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