1-Hydroxybenzotriazole → tert-butyl (2R,5S)-2-[(R)-hydroxy(phenyl)methyl]-5-{4-[(1-oxo-2-oxa-8-azaspiro[4.5]dec-8-yl)carbonyl]benzyl)pyrrolidine-1-carboxylate

HRID 1804648Notes

Reaction equation

HRID 1804648 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@H:13]([OH:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:11][CH2:10][C@H:9]1[CH2:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:31]1(=[O:41])[C:35]2([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH2:34][CH2:33][O:32]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[OH:20][C@H:13]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C@H:12]1[CH2:11][CH2:10][C@@H:9]([CH2:21][C:22]2[CH:30]=[CH:29][C:25]([C:26]([N:38]3[CH2:39][CH2:40][C:35]4([C:31](=[O:41])[O:32][CH2:33][CH2:34]4)[CH2:36][CH2:37]3)=[O:27])=[CH:24][CH:23]=2)[N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 552655722-Oxa-8-azaspiro[4.5]decan-1-oneHCID 670587074-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoic acid

Product 1

HCID 86666757tert-butyl (2R,5S)-2-[(R)-hydroxy(phenyl)methyl]-5-{4-[(1-oxo-2-oxa-8-azaspiro[4.5]dec-8-yl)carbonyl]benzyl)pyrrolidine-1-carboxylateYield 72.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 30 mg (0.07 mmol) 4-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoic acid (i-1) in 1 ml anhydrous DMF at ambient temperature was added 20 mg (0.1 mmol) 2-oxa-8-azaspiro[4.5]decan-1-one, followed by 20 mg (0.1 mmol) EDCl, 15 mg (0.10 mmol) HOBt, and 0.070 ml (0.35 mmol) diisopropylethylamine. The solution was stirred for 2 h. It was then filtered and purified by reverse-phase HPLC (TMC Pro-Pac C18; 35-100% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient). The pure fractions were lyophilized overnight to give 28 mg (70%) of the title compound as a white solid. LC/MS 549.2 (M+1).

Workup

  1. filtrationIt was then filtered
  2. custompurified by reverse-phase HPLC (TMC Pro-Pac C18; 35-100% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient)
  3. waitThe pure fractions were lyophilized overnight

Sources & evidence

ORD record
ord-698bdc3939c64f68afaca95f6f0f69c6
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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