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

HRID 401944Notes

Reaction equation

HRID 401944 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-1572a2c1093b446aae0625eab1e22d57
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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