Sodium hydride → HCID 73331074, compound

HRID 1055267Notes

Reaction equation

HRID 1055267 reaction equation
[CH3:1][C:2]1[N:12]=[C:11]2[N:6]([CH2:7][CH2:8][CH2:9][CH:10]2[OH:13])[C:4](=[O:5])[C:3]=1[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][CH:19]([C:22]2[C:23]3[CH:24]=[CH:25][C:26]([F:31])=[CH:27][C:28]=3[O:29][N:30]=2)[CH2:18][CH2:17]1.C1OCCOCCOCCOCCOCCOC1.Br[CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][C:56]([O:58]CC)=[O:57].[H-].[Na+].C(=O)(O)[O-].[Na+]>C1COCC1>[F:31][C:26]1[CH:25]=[CH:24][C:23]2[C:22]([CH:19]3[CH2:20][CH2:21][N:16]([CH2:15][CH2:14][C:3]4[C:4](=[O:5])[N:6]5[CH2:7][CH2:8][CH2:9][CH:10]([O:13][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][C:56]([OH:58])=[O:57])[C:11]5=[N:12][C:2]=4[CH3:1])[CH2:17][CH2:18]3)=[N:30][O:29][C:28]=2[CH:27]=1

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 2855718-Crown-6HCID 115237PaliperidoneHCID 117544Ethyl 6-bromohexanoateHCID 516892Sodium Bicarbonate

Product 1

HCID 73331074HCID 73331074, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of paliperidone (1.0 g, 2.34 mmol) in THF (15 mL), under argon, was treated with 18-Crown-6 (309.88 mg, 1.17 mmol), ethyl 6-bromohexanoate (628.76 μL, 3.52 mmol) and sodium hydride (60 w/w %, 937.80 mg, 23.45 mmol). After 18 h, the reaction mixture was poured into an aqueous saturated sodium bicarbonate solution (20 mL), and the aqueous layer was extracted with ethyl acetate (three times 20 mL). The aqueous layer was acidified with acetic acid and extracted with 2-methyl THF (three times 20 mL). The combined organic 2-methyl THF layers were dried over Na2SO4, filtered and concentrated. The residue was purified by HPLC to give the title compound. ESI-MS (M+1) 541. 1H NMR: (CDCl3, 360 MHz): δ ppm 1.35-2.00 (m, 11H), δ 2.10-2.30 (m, 8H), δ 2.40-2.80 (m, 8H), δ 3.20-4.00 (m, 5H), δ 4.24-4.30 (m, 1H), δ 7.07 (td, J=8.97, 1.83 Hz, 1H), δ 7.24 (d, J=1.83 Hz, 1H), δ 7.76 (dd, J=8.60, 4.94 Hz, 1H).

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate (three times 20 mL)
  2. extractionextracted with 2-methyl THF (three times 20 mL)
  3. dry with materialThe combined organic 2-methyl THF layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-1d0ac59f547549db9ab0ce1643e4dfdb
Source dataset
uspto-grants-2016_07
Patent number
US09394354B2

Reaction notes

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