Sodium borohydride → 7-Bromo-1,2,3,4-tetrahydro-1,8-naphthyridin-4-ol

HRID 1819106Notes

Reaction equation

HRID 1819106 reaction equation
[Br:1][C:2]1[N:11]=[C:10]2[C:5]([C:6](=[O:12])[CH2:7][CH2:8][NH:9]2)=[CH:4][CH:3]=1.[BH4-].[Na+].C(OCC)(=O)C.CCCCCC>CO>[Br:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]([OH:12])[CH2:7][CH2:8][NH:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 124403577-Bromo-2,3-dihydro-1,8-naphthyridin-4(1H)-oneHCID 21226206Ethyl acetate hexane

Product 1

HCID 578859587-Bromo-1,2,3,4-tetrahydro-1,8-naphthyridin-4-olYield 78%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

7-Bromo-2,3-dihydro-1H-[1,8]naphthyridin-4-one (1.459 g) was placed in methanol (25 mL) and sodium borohydride (437 mg, 1.84 eq) was added portionwise over five (5) minutes. The reaction was stirred at room temperature for 15 minutes and then quenched with acetic acid (3 mL). The reaction mixture was concentrated under reduced pressure and the residue was taken up in toluene (100 mL). Silica gel was added and the mixture was concentrated under reduced pressure. Purification by silica gel chromatography using dry loading and a gradient of 0-80% ethyl acetate/hexane as the eluting solvent gave the title compound as a pale yellow solid (78% yield). M.p. 130-131° C., LCMS: m/z=230.71 (M+H+), 1H-NMR (MeOH-d4, 400 MHz) δ 1.80-1.94 (m, 2H), 3.33-3.48 (m, 2H), 4.66 (t, J=4.4 Hz, 1H), 6.66 (d, J=7.6 Hz, 1H), 7.31 (d, J=7.6 Hz, 1H).

Workup

  1. customquenched with acetic acid (3 mL)
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionSilica gel was added
  4. concentrationthe mixture was concentrated under reduced pressure
  5. customPurification by silica gel chromatography
  6. customusing dry loading

Sources & evidence

ORD record
ord-49331ca9883747ac9de081b40cefd050
Source dataset
uspto-grants-2009_10
Patent number
US07601716B2

Reaction notes

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