1-Hydroxybenzotriazole → {(S)-1-cyclohexyl-2-oxo-2-[(S)-2-(3-phenoxy-phenyl)-pyrrolidine-1-yl]-ethyl}-carbamic acid tert-butyl ester

HRID 222504

Reaction equation

HRID 222504 reaction equation
[O:1]([C:8]1[CH:9]=[C:10]([C@@H:14]2[CH2:18][CH2:17][CH2:16][NH:15]2)[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:19][C:20]([O:23][C:24]([NH:26][C@H:27]([C:34](O)=[O:35])[CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)=[O:25])([CH3:22])[CH3:21].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.[Cl-].[Na+].O>[C:20]([O:23][C:24](=[O:25])[NH:26][C@@H:27]([CH:28]1[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]1)[C:34](=[O:35])[N:15]1[CH2:16][CH2:17][CH2:18][C@H:14]1[C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:9]=1)([CH3:22])([CH3:19])[CH3:21]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 59787976(S)-2-(3-phenoxy-phenyl)-pyrrolidine

Product 1

HCID 59787985{(S)-1-cyclohexyl-2-oxo-2-[(S)-2-(3-phenoxy-phenyl)-pyrrolidine-1-yl]-ethyl}-carbamic acid tert-butyl esterYield 68.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

(S)-2-(3-phenoxy-phenyl)-pyrrolidine (1.2 g, 5.02 mmol) is added to a solution of Boc-L-α-cyclohexylglycine (1.42 g, 5.2 mmol), HOBt (1.0 g, 7.53 mmol) and HBTU (2.86 g, 7.53 mmol) in 10 mL of DMF. Hunig's base (3.6 Ml, 20 mmol) is added and the mixture is stirred for 30 minutes. The mixture is diluted with brine (20 mL) and extracted with EtOAc (3×10 mL). The organics were combined, dried over Na2SO4, filtered, concentrated under reduced pressures and purified by silica gel column chromatography (20% EtOAc/Hexanes) to give {(S)-1-cyclohexyl-2-oxo-2-[(S)-2-(3-phenoxy-phenyl)-pyrrolidine-1-yl]-ethyl}-carbamic acid tert-butyl ester as a white powder (1.65 g, 66%). LCMS m/z 479.2 (M+1).

Workup

  1. extractionextracted with EtOAc (3×10 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressures
  5. custompurified by silica gel column chromatography (20% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-72d8606d0cc04e7c99c8526d137f18a3
Source dataset
uspto-grants-2012_06
Patent number
US08207183B2

Linked notes

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