Lithium Hydroxide → HCID 178425093, compound

HRID 2040328Notes

Reaction equation

HRID 2040328 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:13][C:12]([CH3:15])([CH3:14])[CH2:11][CH2:10][C:9]=2[CH2:16][N:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:55]=[CH:54][C:26]([C:27]([NH:29][S:30]([C:33]4[CH:38]=[CH:37][C:36]([NH:39][CH2:40][C@H:41]5[CH2:46][CH2:45][C@H:44]([C:47]([O:49]C)=[O:48])[CH2:43][CH2:42]5)=[C:35]([N+:51]([O-:53])=[O:52])[CH:34]=4)(=[O:32])=[O:31])=[O:28])=[C:25]([O:56][C:57]4[CH:58]=[C:59]5[CH:65]=[CH:64][NH:63][C:60]5=[N:61][CH:62]=4)[CH:24]=3)[CH2:19][CH2:18]2)=[CH:4][CH:3]=1.[Li+].[OH-]>O1CCCC1.CO.ClCCl.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH2:13][C:12]([CH3:14])([CH3:15])[CH2:11][CH2:10][C:9]=2[CH2:16][N:17]2[CH2:18][CH2:19][N:20]([C:23]3[CH:55]=[CH:54][C:26]([C:27]([NH:29][S:30]([C:33]4[CH:38]=[CH:37][C:36]([NH:39][CH2:40][C@H:41]5[CH2:42][CH2:43][C@H:44]([C:47]([OH:49])=[O:48])[CH2:45][CH2:46]5)=[C:35]([N+:51]([O-:53])=[O:52])[CH:34]=4)(=[O:32])=[O:31])=[O:28])=[C:25]([O:56][C:57]4[CH:58]=[C:59]5[CH:65]=[CH:64][NH:63][C:60]5=[N:61][CH:62]=4)[CH:24]=3)[CH2:21][CH2:22]2)=[CH:6][CH:7]=1

Participants

7

Reactant 2

HCID 3939Lithium HydroxideHCID 178501114HCID 178501114, compound

Product 1

HCID 178425093HCID 178425093, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of EXAMPLE 379B (0.162 g) in tetrahydrofuran (2 mL) and methanol (0.5 mL) was added 1.0 M aqueous LiOH (0.596 mL) and the reaction heated to 50° C. for 1 hour. The reaction was cooled, diluted with dichloromethane (30 mL) and water (5 mL), and quenched with aqueous HCl (1.0 M, 0.6 mL). The aqueous layer was diluted with saturated NH4Cl solution (5 mL) and removed. The organic layer was dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography (Reveleris 40 g) eluting with a gradient of 0.5% to 5% methanol/dichloromethane over 30 minutes (flow=40 mL/minute) provided the title compound. 1H NMR (300 MHz, dimethylsulfoxide-d6) δ 12.00 (s, 1H), 11.68 (s, 1H), 11.38 (s, 1H), 8.55 (d, 2H), 8.04 (d, 1H), 7.79 (dd, 1H), 7.59-7.43 (m, 3H), 7.34 (d, 2H), 7.05 (t, 3H), 6.68 (dd, 1H), 6.39 (dd, 1H), 6.19 (d, 1H), 3.25 (s, 2H), 3.07 (s, 4H), 2.75 (s, 2H), 2.17 (d, 7H), 1.95 (s, 6H), 1.62 (s, 1H), 1.38 (s, 4H), 1.03 (dd, 2H), 0.92 (s, 6H).

Workup

  1. temperatureThe reaction was cooled
  2. customquenched with aqueous HCl (1.0 M, 0.6 mL)
  3. additionThe aqueous layer was diluted with saturated NH4Cl solution (5 mL)
  4. customremoved
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washSilica gel chromatography (Reveleris 40 g) eluting with a gradient of 0.5% to 5% methanol/dichloromethane over 30 minutes (flow=40 mL/minute)

Sources & evidence

ORD record
ord-2749cf22abd9473e894996acf4963fa9
Source dataset
uspto-grants-2013_11
Patent number
US08580794B2

Reaction notes

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