Ammonia → Ammonia

HRID 1972568Notes

Reaction equation

HRID 1972568 reaction equation
CS(O[CH2:6][C@H:7]1[CH2:12][N:11]([S:13]([C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)(=[O:15])=[O:14])[CH2:10][CH2:9][N:8]1[C:21]1[CH:26]=[CH:25][C:24]([C:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=1)(=O)=O.[NH3:34].CO>>[NH3:8].[NH2:34][CH2:6][C@H:7]1[CH2:12][N:11]([S:13]([C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)(=[O:15])=[O:14])[CH2:10][CH2:9][N:8]1[C:21]1[CH:26]=[CH:25][C:24]([C:27]([OH:33])([CH3:32])[C:28]([F:30])([F:31])[F:29])=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 86670301((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate2×

Product 2

HCID 222AmmoniaYield 2%HCID 665825602-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

Conditions

Temperature
140 °C

Procedure

To a 20 mL of microwave vial was added ((2R)-4-(thiophen-2-ylsulfonyl)-1-(4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)piperazin-2-yl)methyl methanesulfonate (1.0 g, 1.9 mmol, Intermediate B) and ammonia, 2M solution in methanol (9.5 mL, 19 mmol, Aldrich, St. Louis, Mo.). The vial was sealed and heated in an Initiator microwave reactor (Biotage AB, Inc., Uppsala, Sweden) at 140° C. for 30 min. The reaction mixture was concentrated and the crude product was purified by column chromatography (80 g of silica gel, 100% CH2Cl2 first then 2 to 5% 2M NH3 in CH2Cl2) to afford 2-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.540 g) as a white foam.

Workup

  1. customThe vial was sealed
  2. concentrationThe reaction mixture was concentrated
  3. customthe crude product was purified by column chromatography (80 g of silica gel, 100% CH2Cl2 first

Sources & evidence

ORD record
ord-5e302612a4a84677bc1270cb0277ea75
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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