1-Hydroxybenzotriazole → {(S)-2-[benzyloxylimino-methyl-pyrrolidine-1-yl]-1-cyclohexyl-2-oxo-ethyl}-carbamic acid tert-butyl ester

HRID 29080Notes

Reaction equation

HRID 29080 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([C:16]([OH:18])=O)[CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:7])([CH3:4])[CH3:3].ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH2:38]([O:45][N:46]=[CH:47][CH:48]1[CH2:52][CH2:51][CH2:50][NH:49]1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>ClCCl>[C:2]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]1)[C:16]([N:49]1[CH2:50][CH2:51][C:47](=[N:46][O:45][CH2:38][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:48]1[CH3:52])=[O:18])([CH3:1])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 72562396Pyrrolidine-2-carbaldehyde-O-benzyl-oxime

Product 1

HCID 86623471{(S)-2-[benzyloxylimino-methyl-pyrrolidine-1-yl]-1-cyclohexyl-2-oxo-ethyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The solution of boc-L-α-cyclohexylglycine (1.27 g, 4.92 mmole), 1-hydroxylbenzotriazole (0.99 g, 7.38 mmole), diisopropylethylamine (2.54 g, 19.68 mmole), and O-benzotriazole-N,N,N,N-tetramethyl-urounium hexafluorophosphate (2.80 g, 7.38 mmole) in dichloromethane (30 ml) is stirred for 15 minutes at room temperature. A solution of pyrrolidine-2-carbaldehyde-O-benzyl-oxime (˜1.00 g, 0.49 mmole) in dichloromethane is added. The reaction solution is stirred for three hours at room temperature and then quenched with saturated NaHCO3 aqueous, extracted with dichloromethane. The organic layer is combined, dried, and concentrated under vacuum. The residue is purified by flash chromatography (silica gel; from 20% to 70% of ethyl acetate in hexane) to provide 1.81 g (83% over 2 steps) of the title compound. M+H+=444.2

Workup

  1. customquenched with saturated NaHCO3 aqueous
  2. extractionextracted with dichloromethane
  3. customdried
  4. concentrationconcentrated under vacuum
  5. customThe residue is purified by flash chromatography (silica gel; from 20% to 70% of ethyl acetate in hexane)

Sources & evidence

ORD record
ord-71d78ba436c044e7892fe799b4ab8c95
Source dataset
uspto-grants-2008_09
Patent number
US07419975B2

Reaction notes

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