Acetic Acid → 1,1,1-Trifluoro-2-(4-(2-(4-morpholinylmethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

HRID 1972422Notes

Reaction equation

HRID 1972422 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([OH:27])([CH3:26])[C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[CH:11]([CH:28]=O)[CH2:10]1)(=[O:8])=[O:7].[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl>[F:25][C:22]([F:23])([F:24])[C:21]([C:18]1[CH:17]=[CH:16][C:15]([N:12]2[CH2:13][CH2:14][N:9]([S:6]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)(=[O:7])=[O:8])[CH2:10][CH:11]2[CH2:28][N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[CH:20][CH:19]=1)([OH:27])[CH3:26]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 866703254-(2-Thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinecarbaldehyde

Product 1

HCID 569322681,1,1-Trifluoro-2-(4-(2-(4-morpholinylmethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanolYield 9.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinecarbaldehyde (45 mg, 0.100 mmol) and morpholine (26.2 mg, 0.301 mmol, Aldrich, St. Louis, Mo.) in 1,2-dichloroethane (2.0 mL) was added sodium triacetoxyborohydride (106 mg, 0.502 mmol) and acetic acid (5.74 μL, 0.100 mmol). The reaction was stirred at room temperature for 1 h then quenched with methanol (5 mL) and concentrated. The crude material was dissolved in methanol, filtered and purified using prep HPLC (Phenomenex C18 column (150×30 mm) eluting with TFA in CH3CN/H2O (10% to 90% gradient over 25 min) at a 30 mL/min flow rate) to yield 1,1,1-trifluoro-2-(4-(2-(4-morpholinylmethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (5 mg) as a mixture of four isomers.

Workup

  1. customthen quenched with methanol (5 mL)
  2. concentrationconcentrated
  3. dissolutionThe crude material was dissolved in methanol
  4. filtrationfiltered
  5. custompurified
  6. washeluting with TFA in CH3CN/H2O (10% to 90% gradient over 25 min) at a 30 mL/min flow rate)

Sources & evidence

ORD record
ord-99a25d8a9dd7474cb5c55a751ad55eee
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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