Sodium Hydroxide → HCID 44546742, compound

HRID 1967427Notes

Reaction equation

HRID 1967427 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:22]=[CH:23][CH:24]=1)[CH2:6][N:7]([CH3:21])[CH2:8][CH:9]([C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=1)O.[OH-].[Na+]>ClCCl.CS(O)(=O)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:22]([CH:9]([C:11]3[CH:20]=[CH:19][C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[CH:12]=3)[CH2:8][N:7]([CH3:21])[CH2:6]2)=[CH:23][CH:24]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 44546739HCID 44546739, compound

Product 1

HCID 44546742HCID 44546742, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6395Methanesulfonic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of the alcohol, Compound 5, (495 g, 1.54 mol) in dichloromethane (6.0 L) was split equally into two flasks. To each half of the ice-cold solution was added methanesulfonic acid (500 mL, 7.7 mmol) via additional funnel (˜1 h). The reaction solution was allowed to slowly warm to room temperature and stirred for 6-8 h before it was cooled to <10° C. and quenched slowly with an aqueous solution of sodium hydroxide (330 g, 8.3 mol in 600 mL of water). The internal temperature during the addition was kept less than 30° C. The organic layer was then separated, washed with water, dried over sodium sulfate and concentrated in vacuo. The crude product from the two batches were combined and purified by flash column chromatography (hexanes/ethyl acetate 88:12 to ethyl acetate/methanol 99.9:0.1) to give Compound 6 (280.4 g, 60% over 4 steps) as a thick oil: 1H NMR (500 MHz, CDCl3) δ 7.81-7.74 (m, 3H), 7.68 (s, 1H), 7.47-7.42 (m, 2H), 7.28-7.26 (m, 1H), 6.79 (d, J=8.5 Hz, 1H), 6.80-6.62 (m, 2H), 4.40 (dd, J=8.5, 6.0 Hz, 1H), 3.80-3.78 (m, 1H), 3.77 (s, 3H), 3.65 (d, J=15.0 Hz, 1H), 3.11-3.08 (m, 1H), 2.65 (dd, J=11.5, 6.0 Hz, 1H), 2.45 (s, 3H); ESI MS m/z 304 [M+H]+.

Workup

  1. temperaturewas cooled to <10° C.
  2. additionThe internal temperature during the addition
  3. customwas kept less than 30° C
  4. customThe organic layer was then separated
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. custompurified by flash column chromatography (hexanes/ethyl acetate 88:12 to ethyl acetate/methanol 99.9:0.1)

Sources & evidence

ORD record
ord-d890c667090c40a7a4a7fb783f16791c
Source dataset
uspto-grants-2013_04
Patent number
US08420811B2

Reaction notes

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