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

HRID 1972583Notes

Reaction equation

HRID 1972583 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(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[F:25][C:24]([F:26])([F:27])[C:23]([C:20]1[CH:19]=[CH:18][C:17]([N:4]2[CH2:5][CH2:6][N:7]([S:9]([C:12]3[S:13][CH:14]=[CH:15][CH:16]=3)(=[O:10])=[O:11])[CH2:8][C@@H:3]2[CH2:2][NH:1][CH:32]2[CH2:33][O:30][CH2:31]2)=[CH:22][CH:21]=1)([OH:29])[CH3:28]

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 665824081,1,1-trifluoro-2-(4-((2S)-2-((3-oxetanylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanolYield 69.7%

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 (0.300 g, 0.667 mmol, Example 192, Step 1) in CH2Cl2 (5.0 mL) was added 3-oxetanone (0.050 mL, 0.67 mmol, Aldrich, St. Louis, Mo.), 4 molecular sieves (75 mg), and acetic acid (0.01 mL, 0.1 mmol). After stirred for 30 min, sodium triacetoxyborohydride (0.425 g, 2.01 mmol) was added and the reaction mixture was continued to stir at room temperature for 1 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 layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (80 g of silica gel, 2 to 5% 2M NH3 in MeOH/CH2Cl2) to afford 1,1,1-trifluoro-2-(4-((2S)-2-((3-oxetanylamino)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (0.235 g) as a mixture of two isomers:

Workup

  1. stirringto stir at room temperature for 1 h
  2. customThe reaction mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and CH2Cl2 (40 mL)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (2×15 mL)
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (80 g of silica gel, 2 to 5% 2M NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ba9c4f4f526944809dc0d09514a25a58
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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