Diethyl Ether → HCID 59746638, compound

HRID 601714Notes

Reaction equation

HRID 601714 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:39]=[C:40]([F:42])[CH:41]=1)[CH2:5][C@H:6]1[C@@H:10]([C@H:11]2[CH2:20][C:19]3[C:14](=[C:15]([O:21][CH2:22][CH:23]=[CH2:24])[CH:16]=[CH:17][CH:18]=3)[CH2:13][N:12]2[CH:25]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[O:9]C(=O)[NH:7]1.[Li+].[OH-].C(OCC)C>CCO.O>[CH2:22]([O:21][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:14]=1[CH2:13][N:12]([CH:25]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C@@H:11]([C@@H:10]([OH:9])[C@@H:6]([NH2:7])[CH2:5][C:4]1[CH:39]=[C:40]([F:42])[CH:41]=[C:2]([F:1])[CH:3]=1)[CH2:20]2)[CH:23]=[CH2:24]

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 3939Lithium HydroxideHCID 67271283HCID 67271283, compound

Product 1

HCID 59746638HCID 59746638, compoundYield 105.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((R)-8-(allyloxy)-2-benzhydryl-1,2,3,4-tetrahydroisoquinolin-3-yl)oxazolidin-2-one (Step F (15), 40 mg, 0.07 mmol) in EtOH (3 mL) was added a solution of LiOH (17 mg, 0.7 mmol) in H2O (0.6 mL). This reaction mixture was stirred at 110° C. for 5 h and stirred at 80° C. overnight. Ethyl ether (50 mL) was added to the mixture and washed with 1N HCl (40 mL) twice. The aqueous phase was basified to pH 12 with 50% aqueous NaOH solution. This mixture was extracted with ethyl acetate (120 mL). The organic layer was dried (Na2SO4), and concentrated in vacuo to give 40 mg of the title compound of Preparation F. 1H NMR (CDCl3, 500 MHz) δ 1.87 (3H, brd s), 2.38 (1H, dd, J=10, 15 Hz), 2.79 (1H, d, J=20 Hz), 2.96-2.99 (2H, m), 3.05 (1H, dd, J=5, 15 Hz), 3.62 (1H, m), 3.66 (1H, dd, J=5, 10 Hz), 3.71 (1H, d, J=20 Hz), 4.04 (1H, d, J=15 Hz), 4.33-4.40 (2H, m), 4.77 (1H, s), 5.08-5.15 (2H, m), 5.81 (1H, m), 6.63 (1H, d, J=10 Hz), 6.71-6.75 (1H, m), 6.79 (1H, d, J=10 Hz), 6.88 (2H, m), 7.10-7.21 (5H, m), 7.28-7.31 (2H, m), 7.40 (2H, d, J=10 Hz), 7.44 (2H, d, J=5 Hz). MS (ESI) (M+H)+ 541.22.

Workup

  1. stirringstirred at 80° C. overnight
  2. washwashed with 1N HCl (40 mL) twice
  3. extractionThis mixture was extracted with ethyl acetate (120 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto give

Sources & evidence

ORD record
ord-36513af75b034493af82f157e833eee7
Source dataset
uspto-grants-2011_03
Patent number
US07902218B2

Reaction notes

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