Acetic Acid → 2-(4-((2S)-2-((di-3-oxetanylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

HRID 1972582Notes

Reaction equation

HRID 1972582 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:8][N:7]([S:9]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)(=[O:11])=[O:10])[CH2:6][CH2:5][N:4]1[C:17]1[CH:22]=[CH:21][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=1.[O:30]1[CH2:33][C:32](=O)[CH2:31]1.[C:35]([OH:38])(=O)[CH3:36].[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[O:38]1[CH2:35][CH:36]([N:1]([CH2:2][C@H:3]2[CH2:8][N:7]([S:9]([C:12]3[S:13][CH:14]=[CH:15][CH:16]=3)(=[O:10])=[O:11])[CH2:6][CH2:5][N:4]2[C:17]2[CH:18]=[CH:19][C:20]([C:23]([OH:29])([CH3:28])[C:24]([F:26])([F:27])[F:25])=[CH:21][CH:22]=2)[CH:32]2[CH2:31][O:30][CH2:33]2)[CH2:39]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 150242543-OxetanoneHCID 665825602-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

Product 1

HCID 569328252-(4-((2S)-2-((di-3-oxetanylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanolYield 121.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.380 g, 0.845 mmol, Example 192, Step 1) in CH2Cl2 (8.0 mL) was added 3-oxetanone (0.20 mL, 2.5 mmol, Aldrich, St. Louis, Mo.), 4 molecular sieves (75 mg), acetic acid (0.015 mL, 0.17 mmol) and sodium triacetoxyborohydride (0.717 g, 3.38 mmol). The resulting mixture was stirred at room temperature for 15 h. The reaction mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and CH2Cl2 (40 mL). The aqueous layer was extracted with CH2Cl2 (2×15 mL) and the combined organic extracts were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (80 g of silica gel, 2 to 5% MeOH in CH2Cl2) to afford 2-(4-((2S)-2-((di-3-oxetanylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.116 g) as a mixture of two isomers:

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and CH2Cl2 (40 mL)
  2. extractionThe aqueous layer was extracted with CH2Cl2 (2×15 mL)
  3. dry with materialthe combined organic extracts were dried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (80 g of silica gel, 2 to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-8deb4e6c6c0f43d6b04816936ba548ed
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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