Triethylamine → (R)-1'-[2-(1-Butyryloxy-ethyl)-pyrimidin-4-yl]-6-chloro-spiro[chroman-2,4'-piperidin]-4-one

HRID 394514Notes

Reaction equation

HRID 394514 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:15](=[CH:16][CH:17]=1)[O:14][C:8]1([CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[CH2:7][C:6]2=[O:18].[C:19]([O:24][C@@H:25]([C:27]1[N:32]=[C:31](Cl)[CH:30]=[CH:29][N:28]=1)[CH3:26])(=[O:23])[CH2:20][CH2:21][CH3:22].C(N(CC)CC)C>C(O)(C)C>[C:19]([O:24][C@@H:25]([C:27]1[N:28]=[C:29]([N:11]2[CH2:12][CH2:13][C:8]3([CH2:7][C:6](=[O:18])[C:5]4[C:15](=[CH:16][CH:17]=[C:3]([Cl:2])[CH:4]=4)[O:14]3)[CH2:9][CH2:10]2)[CH:30]=[CH:31][N:32]=1)[CH3:26])(=[O:23])[CH2:20][CH2:21][CH3:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10944226(R)-1-(4-chloro-pyrimidin-2-yl)ethyl butyrateHCID 223286586-Chlorospiro[chroman-2,4'-piperidin]-4-one hydrochloride

Product 1

HCID 54550021(R)-1'-[2-(1-Butyryloxy-ethyl)-pyrimidin-4-yl]-6-chloro-spiro[chroman-2,4'-piperidin]-4-oneYield 100%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of 6-chloro-spiro[chroman-2,4′-piperidin]-4-one hydrochloride (prepared according to the method of Example 78, Step A, 175 mg, 0.61 mmol) in isopropanol (5 mL) was added (R)-1-(4-chloro-pyrimidin-2-yl)-ethyl butyrate (prepared according to the method of Preparation Seven, 160 mg, 0.70 mmol) followed by triethylamine (0.29 mL, 2.1 mmol). This mixture was stirred at reflux for 1.5 h, concentrated, and purified by flash column chromatography (1% methanol/chloroform) to give 270 mg (100%) of the title compound of Example 78, Step B as a yellow oil. 1H NMR (CDCl3, 400 MHz) δ 8.19 (d, 1H), 7.83 (d, 1H), 7.44 (dd, 1H), 6.97 (d, 1H), 6.37 (d, 1H), 5.64 (q, 1H), 4.18 (app s, 2H), 3.34 (t, 2H), 2.72 (s, 2H), 2.37 (t, 2H), 2.10 (d, 2H), 1.71-1.60 (c, 4H), 1.55 (d, 3H), 0.94 (t, 3H); MS (APCI) 444, 446 (MH+).

Workup

  1. customprepared
  2. customaccording to the method of Preparation Seven, 160 mg, 0.70 mmol)
  3. temperatureat reflux for 1.5 h
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (1% methanol/chloroform)

Sources & evidence

ORD record
ord-468f3cb68d804616893ac760d47c9a20
Source dataset
uspto-grants-2003_08
Patent number
US06602875B2

Reaction notes

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