Potassium tert-butoxide → (+/-)-trans-4-[6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-3-fluoro-piperidine-1-carboxylic acid benzyl ester

HRID 1971950Notes

Reaction equation

HRID 1971950 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C@@H:14]([OH:17])[C@H:13]([F:18])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].[CH2:25]([C:29]1[N:30]=[N:31][C:32](Cl)=[CH:33][C:34]=1[C:35]1[CH:40]=[CH:39][C:38]([O:41][CH:42]2[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]2)=[CH:37][CH:36]=1)[CH2:26][CH2:27][CH3:28]>C1COCC1.CCOC(C)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C@@H:14]([O:17][C:32]2[N:31]=[N:30][C:29]([CH2:25][CH2:26][CH2:27][CH3:28])=[C:34]([C:35]3[CH:36]=[CH:37][C:38]([O:41][CH:42]4[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]4)=[CH:39][CH:40]=3)[CH:33]=2)[C@H:13]([F:18])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 52324488benzyl (3R,4R)-3-fluoro-4-hydroxypiperidine-1-carboxylateHCID 866577793-Butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine

Product 1

HCID 86657795(+/-)-trans-4-[6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-3-fluoro-piperidine-1-carboxylic acid benzyl esterYield 34%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of (±)-trans-3-fluoro-4-hydroxy-piperidine-1-carboxylic acid benzyl ester (100 mg, 0.4 mmol) at 0° C. in THF (2 mL) was added potassium tert-butoxide (1.0 M in THF, 0.5 mmol, 0.5 mL). After 15 min 3-butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine (120 mg, 0.34 mmol) in THF (2 mL) was added. The solution was stirred overnight at 40° C., diluted with EtOAc and washed with water. The organics were dried over sodium sulfate, filtered, concentrated, and purified by column chromatography using 20-40% EtOAc in hexanes to provide (±)-trans-4-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-3-fluoro-piperidine-1-carboxylic acid benzyl ester (65 mg).

Workup

  1. washwashed with water
  2. dry with materialThe organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-b53d48d96a4c4c1ea4b527314e9ca2b8
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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