Hydrochloric Acid → HCID 44828663, compound

HRID 2062276Notes

Reaction equation

HRID 2062276 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([CH2:14][NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:9]1)=O)(C)(C)C.[ClH:26].O1CCOCC1>>[ClH:26].[NH:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([CH2:14][NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:9]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 45158795(S)-1-Boc-3-(Cbz-amino-methyl)-piperidine

Product 1

HCID 44828663HCID 44828663, compound

Procedure

Benzyl ((S)-1-(tert-butoxycarbonyl)piperidin-3-yl)methylcarbamate (1.2 g, 3.54 mmol) was treated with 4.0 M HCl solution in dioxane (4.3 mL, 17.2 mmol). Formation of a white precipitate was observed. The reaction was complete after three hours. The solvent and excess HCl were removed under reduced pressure to obtain benzyl ((S)-piperidin-3-yl)methylcarbamate hydrochloride as a white solid. This solid was suspended in DMF/CH2Cl2 (3 mL/3 mL), followed by the addition of 2-(4-chloro-7-methylquinazolin-2-yl)phenol (958 mg, 3.54 mmol) and then triethylamine (1.8 mL, 1.3 g, 12.85 mmol). The mixture was stirred at room temperature under an N2 atmosphere for 16 h. The reaction was then partitioned between H2O and CH2Cl2, separated, and the aqueous layer was extracted twice with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography using 0-5% MeOH in CH2Cl2 gave benzyl((R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate as a thick yellow oil (855 mg, 51%). LC/MS: m/z 483.5 (M+H)+ at 2.81 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customThe solvent and excess HCl were removed under reduced pressure

Sources & evidence

ORD record
ord-6f817d8561754970a67641f0ce213b70
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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