Sodium bis(trimethylsilyl)amide → 8-(cyclopropylmethoxy)-4-hydroxy-7-methoxyquinolin-2(1H)-one

HRID 1095786Notes

Reaction equation

HRID 1095786 reaction equation
[C:1]([NH:4][C:5]1[C:14]([O:15][CH2:16][CH:17]2[CH2:19][CH2:18]2)=[C:13]([O:20][CH3:21])[CH:12]=[CH:11][C:6]=1[C:7](OC)=[O:8])(=[O:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>O1CCCC1>[CH:17]1([CH2:16][O:15][C:14]2[C:13]([O:20][CH3:21])=[CH:12][CH:11]=[C:6]3[C:5]=2[NH:4][C:1](=[O:3])[CH:2]=[C:7]3[OH:8])[CH2:19][CH2:18]1

Participants

4

Reactant 2

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 53441632Methyl 2-acetamido-3-(cyclopropylmethoxy)-4-methoxybenzoate

Product 1

HCID 573636778-(cyclopropylmethoxy)-4-hydroxy-7-methoxyquinolin-2(1H)-oneYield 84.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 2-acetamido-3-(cyclopropylmethoxy)-4-methoxybenzoate (93%, 55 g, 175 mmol) and tetrahydrofuran (500 mL) was added dropwise (internal temperature kept below −65° C.) to a solution of sodium bis(trimethylsilyl)amide (NaHMDS) (691 mL, 1M toluene, 691 mmol) at −78° C. under N2. The cooling bath was removed, and the reaction was stirred overnight. The reaction was quenched with water/ice (1 L) and washed with diethyl ether (300 mL×2). The aqueous phase was adjusted to pH=3, with 6 N HCl. The resulting solids were collected by filtration, washed with water (500 mL×2), and dried in an oven to give 38.8 g of 8-(cyclopropylmethoxy)-4-hydroxy-7-methoxyquinolin-2(1H)-one as a yellow solid. MS (ESI): 262.0.

Workup

  1. customThe cooling bath was removed
  2. customThe reaction was quenched with water/ice (1 L)
  3. washwashed with diethyl ether (300 mL×2)
  4. filtrationThe resulting solids were collected by filtration
  5. washwashed with water (500 mL×2)
  6. customdried in an oven

Sources & evidence

ORD record
ord-371fdfe92a7b433daddd00f3953be2c4
Source dataset
uspto-grants-2012_03
Patent number
US08138205B2

Reaction notes

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