Sodium hydride → (E)-(2-(2-(2-(4-(1-(3-(6-Bromopyridin-2-yl)acrylamido)butyl)phenoxy)ethoxy)ethoxy)ethyl)imidodicarbonic acid, 1,3-bis-tert-butyl ester

HRID 2406600Notes

Reaction equation

HRID 2406600 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]([NH:14][CH:15]([C:19]1[CH:48]=[CH:47][C:22]([O:23][CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][N:32]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:21][CH:20]=1)[CH2:16][CH2:17][CH3:18])=[O:13])(OCC)=O)C.[Br:49][C:50]1[N:55]=[C:54]([CH:56]=O)[CH:53]=[CH:52][CH:51]=1>O1CCCC1>[Br:49][C:50]1[N:55]=[C:54](/[CH:56]=[CH:11]/[C:12]([NH:14][CH:15]([C:19]2[CH:20]=[CH:21][C:22]([O:23][CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][N:32]([C:40]([O:42][C:43]([CH3:44])([CH3:46])[CH3:45])=[O:41])[C:33]([O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[O:34])=[CH:47][CH:48]=2)[CH2:16][CH2:17][CH3:18])=[O:13])[CH:53]=[CH:52][CH:51]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27570096-Bromopyridine-2-carbaldehydeHCID 86762604(2-(2-(2-(4-(1-(2-(Diethoxyphosphoryl)acetamido)butyl)phenoxy)ethoxy)ethoxy)ethyl)imidodicarbonic acid, 1,3-bis-tert-butyl ester

Product 1

HCID 86762605(E)-(2-(2-(2-(4-(1-(3-(6-Bromopyridin-2-yl)acrylamido)butyl)phenoxy)ethoxy)ethoxy)ethyl)imidodicarbonic acid, 1,3-bis-tert-butyl esterYield 67.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of NaH (52 mg 60% in mineral oil, 1.31 mmol) in tetrahydrofuran (1.0 mL) at ice bath temperature was added a solution of (2-(2-(2-(4-(1-(2-(diethoxyphosphoryl)acetamido)butyl)phenoxy)ethoxy)ethoxy)ethyl)imidodicarbonic acid, 1,3-bis-tert-butyl ester (49; 295 mg, 0.43 mmol) in tetrahydrofuran (2 mL). The resulting mixture was stirred at room temperature for 30 minutes and then treated drop-wise with 6-bromopicolinaldehyde (81 mg, 0.43 mmol) in tetrahydrofuran (2 mL). The mixture was stirred for another 30 minutes, and then carefully quenched with water. The solution was extracted with ethyl acetate (3×), and the combined organic extracts were washed with sat. brine, dried over sodium sulfate, and concentrated to an oil. Purification by flash silica gel column chromatography, eluting with 7:3 hexanes/ethyl acetate, afforded 50 (205 mg, 67%) as a clear oil: MS (ES+) m/z 706.2 (M+H)+.

Workup

  1. stirringThe mixture was stirred for another 30 minutes
  2. customcarefully quenched with water
  3. extractionThe solution was extracted with ethyl acetate (3×)
  4. washthe combined organic extracts were washed with sat. brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to an oil
  7. customPurification by flash silica gel column chromatography
  8. washeluting with 7:3 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-293e2a258ec349dc847e2ffcb0187a66
Source dataset
uspto-grants-2014_08
Patent number
US08809377B2

Reaction notes

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