Triphenylphosphine → HCID 178498397, compound

HRID 525426Notes

Reaction equation

HRID 525426 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][N:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][CH2:14]1)[N:6]=[CH:5]2.[C:23]([C@@H:27]1[CH2:32][CH2:31][C@H:30](O)[CH2:29][CH2:28]1)([CH3:26])([CH3:25])[CH3:24].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O.C1COCC1>[C:23]([C@H:27]1[CH2:32][CH2:31][C@H:30]([O:1][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([CH2:12][N:13]2[CH2:14][CH2:15][CH:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:17][CH2:18]2)[N:6]=[CH:5]3)[CH2:29][CH2:28]1)([CH3:26])([CH3:25])[CH3:24]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 68279500Methyl 1-((6-hydroxyquinazolin-2-yl)methyl)piperidine-4-carboxylateHCID 178445811HCID 178445811, compound

Product 1

HCID 178498397HCID 178498397, compoundYield 284.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Into a 25 mL round bottom flask was added methyl 1-((6-hydroxyquinazolin-2-yl)methyl)piperidine-4-carboxylate (0.5 g, 1.6 mmol), cis-4-tert-butylcyclohexanol (0.38 g, 0.24 mmol, 1.5 eq), PPh3 (0.87 g, 3.3 mmol, 2 eq) and dry THF (0.5 mL) under N2 atmosphere. Then DIAD (0.53 g, 0.33 mmol, 2 eq) was quickly added in one portion at room temperature. The reaction mixture was stirred at rt for 0.5 h, diluted with water (20 mL) and extracted with DCM (20 ml*3). The combined organic lays were dried over MgSO4 and concentrated. The residue was purified by prep-TLC (DCM/MeOH=15/1) to give methyl 1-((6-(trans-4-tert-butylcyclohexyloxy)quinazolin-2-yl)methyl)piperidine-4-carboxylate (300 mg, yield: 20%) as brown oil. 1HNMR (400 MHz, CDCl3) δ: 9.27 (s, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.45 (dd, J=8.8, 2.8 Hz, 1H), 7.07 (d, J=2.8 Hz, 1H), 4.30˜4.20 (m, 1H), 3.94 (s, 2H), 3.59 (s, 3H), 3.00˜2.98 (m, 2H), 2.28˜2.18 (m, 4H), 1.85-1.82 (m, 6H), 1.40˜1.34 (m, 2H), 1.18˜1.03 (m, 4H), 0.86 (s, 9H); ESI-MS: m/z 440.1 (M+1)+.

Workup

  1. extractionextracted with DCM (20 ml*3)
  2. dry with materialThe combined organic lays were dried over MgSO4
  3. concentrationconcentrated
  4. customThe residue was purified by prep-TLC (DCM/MeOH=15/1)

Sources & evidence

ORD record
ord-d7f1ca42d0414d2d81e181f2d5fe91a9
Source dataset
uspto-grants-2016_05
Patent number
US09340527B2

Reaction notes

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