Sodium Hydroxide → (2S)-2-((3R)-3-(4-(2-methoxyphenyl)piperidin-1-yl)-2-cyclopropylpyrrolidin-1-yl)-2-phenylethanol

HRID 406490Notes

Reaction equation

HRID 406490 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH:11]1([C@@:14]23[C@H:21]([N:22]4[CH2:27][CH2:26][CH:25]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[O:34][CH3:35])[CH2:24][CH2:23]4)[CH2:20][C:19](=O)[N:18]2[C@@H:17]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:16][O:15]3)[CH2:13][CH2:12]1.[OH-].[Na+]>C1COCC1.CCOCC.O>[CH3:35][O:34][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[CH:25]1[CH2:24][CH2:23][N:22]([C@@H:21]2[CH2:20][CH2:19][N:18]([C@@H:17]([C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH2:16][OH:15])[CH:14]2[CH:11]2[CH2:13][CH2:12]2)[CH2:27][CH2:26]1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 6451240Aluminum(III) ChlorideHCID 21226445Aluminium lithium hydrideHCID 59764769HCID 59764769, compound

Product 1

HCID 59764970(2S)-2-((3R)-3-(4-(2-methoxyphenyl)piperidin-1-yl)-2-cyclopropylpyrrolidin-1-yl)-2-phenylethanolYield 100%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To solid aluminum chloride (0.422 g, 3.16 mmol) at 0° C. was added anhydrous THF (23 mL). The mixture was stirred until all solid went into solution. Lithium aluminum hydride (1.0 N in THF, 8.95 mL, 8.95 mmol) was added dropwise and the reaction mixture was allowed to warm to room temperature. After about 20 minutes, the reaction mixture was cooled to about −78° C. and a solution of (3S,7R,7aR)-7a-cyclopropyl-7-(4-(2-methoxyphenyl)piperidin-1-yl)-3-phenyltetrahydropyrrolo[2,1-b]oxazol-5(6H)-one (preparation #25) (1.29 g, 2.98 mmol) in THF (16 mL) was added. The reaction mixture was stirred for about 1 h then allowed to warm up to room temperature and stirred for an additional 3 h. The reaction mixture was cooled to about 0° C. and water (2.7 mL) was added dropwise followed by aqueous NaOH (2.0N, 4 mL). More water (9 mL) was added, then ether (70 mL) and the mixture was stirred for about 30 min. The ether solution was decanted, dried over MgSO4 and concentrated in vacuo to afford (2S)-2-((3R)-3-(4-(2-methoxyphenyl)piperidin-1-yl)-2-cyclopropylpyrrolidin-1-yl)-2-phenylethanol (1.25 g, 2.98 mmol) as a pair of diastereomers as a white solid. RP-HPLC (Table 1, Method a) Rt 1.79 and 1.96 min; m/z: (M+H)+ 421.

Workup

  1. temperaturethe reaction mixture was cooled to about −78° C.
  2. stirringThe reaction mixture was stirred for about 1 h
  3. temperatureto warm up to room temperature
  4. stirringstirred for an additional 3 h
  5. temperatureThe reaction mixture was cooled to about 0° C.
  6. customThe ether solution was decanted
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-303560a278144596bdf158cc2f64e1c3
Source dataset
uspto-grants-2014_06
Patent number
US08754107B2

Reaction notes

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