2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → HCID 86635964, compound

HRID 1698524Notes

Reaction equation

HRID 1698524 reaction equation
C([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([C@H:21]([NH:35][C:36](=[O:48])[C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[C:38]=2[Cl:47])[C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH2:31][CH:32]3[CH2:34][CH2:33]3)(=[O:30])=[O:29])=[CH:24][CH:23]=2)[CH2:10]1)C1C=CC=CC=1.C(O[C@H]1CN(C(OC(C)(C)C)=O)[C@H](C(O)=O)C1)C1C=CC=CC=1.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N.C1CC=CCC=1>CCOCC.O.ClCCCl>[Cl:47][C:38]1[C:39]([C:43]([F:45])([F:44])[F:46])=[CH:40][CH:41]=[CH:42][C:37]=1[C:36]([NH:35][C@H:21]([C:22]1[CH:27]=[CH:26][C:25]([S:28]([CH2:31][CH:32]2[CH2:33][CH2:34]2)(=[O:29])=[O:30])=[CH:24][CH:23]=1)[C@@H:11]1[CH2:10][C@@H:9]([OH:8])[CH2:13][N:12]1[C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])=[O:48]

Participants

8

Reactant 4

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 123431,4-CyclohexadieneHCID 11860409Boc-Hyp(Bzl)-OHHCID 67275776HCID 67275776, compound

Product 1

HCID 86635964HCID 86635964, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of tert-butyl (2S,4R)-4-(benzyloxy)-2-((R)-{[2-chloro-3-(trifluoromethyl)benzoyl]amino}{4-[(cyclopropylmethyl)sulfonyl]phenyl}methyl)-pyrrolidine-1-carboxylate (330 mg, 0.49 mmol) prepared from (2S,4R)-4-(benzyloxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid using the method outlined for Examples 11-46, DDQ (0.78 g, 3.4 mmol), DCE (25 mL) and water (1.5 mL) was stirred at 60° C. for 10 hours. After cooling to rt, 1,4-cyclohexadiene (0.76 ml) was added. The mixture was stirred for 5 min. and diluted with ether (70 ml). The mixture was washed with sat. aq. NaHCO3. The organic extract was dried and concentrated. The residue purified by preparative TLC (DCM:MeOH 10%) to give the title product (150 mg, 50%). 1H NMR (CDCl3) δ (ppm) 9.77 (1H, d, J=5.9 Hz), 7.92 (2H, d, J=8.2 Hz), 7.76 (1H, d, J=7.5 Hz), 7.65 (1H, d, J=6.8 Hz), 7.54 (2H, t, J=8.0 Hz), 7.43 (1H, t, J=7.6 Hz), 5.12 (1H, d, J=6.4 Hz), 4.56 (1H, t, J=7.9 Hz), 3.92 (1H, br s), 3.40 (1H, d, J=12.2 Hz), 3.07-2.97 (2H, m), 2.52 (1H, dd, J=8.6 and 3.8 Hz), 2.32-2.22 (1H, m), 1.93-1.87 (1H, m), 1.49 (9H, s), 1.01 (1H, m), 0.57 (2H, m), 0.14 (2H, m).

Workup

  1. temperatureAfter cooling to rt
  2. stirringThe mixture was stirred for 5 min.
  3. washThe mixture was washed with sat. aq. NaHCO3
  4. extractionThe organic extract
  5. customwas dried
  6. concentrationconcentrated
  7. customThe residue purified by preparative TLC (DCM:MeOH 10%)

Sources & evidence

ORD record
ord-81c78e8522c946019ae7625e4c3c44db
Source dataset
uspto-grants-2012_04
Patent number
US08163956B2

Reaction notes

Loading…