Water → HCID 136121342, compound

HRID 2062285Notes

Reaction equation

HRID 2062285 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[N:3]=1.[NH:20]1[CH2:25][CH2:24][CH:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22][CH2:21]1.C(N(CC)CC)C.O>ClCCl>[OH:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:4]1[N:3]=[C:2]([N:20]2[CH2:21][CH2:22][CH:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:24][CH2:25]2)[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 7238334-(N-Boc-amino)piperidineHCID 1361050322-(4-Chloro-7-methylquinazolin-2-yl)-phenol

Product 1

HCID 136121342HCID 136121342, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a cooled (0-5° C.) suspension of 2-(4-chloro-7-methylquinazolin-2-yl)phenol (50.2 g, 186 mmol) in dichloromethane (200 mL) was slowly added a solution of tert-butyl piperidin-4-ylcarbamate (39.0 g, 195 mmol) and triethylamine (56 mL, 390 mmol) in dichloromethane (200 mL). The resulting mixture was stirred overnight at room temperature. Water (400 ml) was added, and the layers were separated. The aqueous layer was extracted with dichloromethane (2×200 mL), and the combined organic layers were dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The residue was purified by column chromatography (SiO2, eluent: dichloromethane/heptanes 4:6-1:0). Two fractions were obtained: 38.7 g of tert-butyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-4-ylcarbamate as a yellow solid, and a less pure fraction (26.1 g) that was purified by recrystallization from methanol to yield tert-butyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-4-ylcarbamate. Both fractions were combined (17.0 g, 69%).

Workup

  1. temperatureTo a cooled
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with dichloromethane (2×200 mL)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness under reduced pressure
  7. customThe residue was purified by column chromatography (SiO2, eluent: dichloromethane/heptanes 4:6-1:0)
  8. customTwo fractions were obtained
  9. custom38.7 g of tert-butyl 1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-4-ylcarbamate as a yellow solid, and a less pure fraction (26.1 g) that was purified by recrystallization from methanol

Sources & evidence

ORD record
ord-bebbe6c84efb41f5a8818e672ee73667
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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