Hydrochloric Acid → ((R)-2-Hydroxymethyl-piperazin-1-yl)-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanone, hydrochloride

HRID 572296

Reaction equation

HRID 572296 reaction equation
[CH3:1][C:2]1[C:3]([C:11]2[S:15][C:14]([C:16]([OH:18])=O)=[CH:13][CH:12]=2)=[N:4][O:5][C:6]=1[C:7]([F:10])([F:9])[F:8].C([N:26]1[CH2:31][CH2:30][NH:29][C@@H:28]([CH2:32][OH:33])[CH2:27]1)(OC(C)(C)C)=O.[ClH:34]>O1CCOCC1>[ClH:34].[OH:33][CH2:32][C@H:28]1[CH2:27][NH:26][CH2:31][CH2:30][N:29]1[C:16]([C:14]1[S:15][C:11]([C:3]2[C:2]([CH3:1])=[C:6]([C:7]([F:8])([F:9])[F:10])[O:5][N:4]=2)=[CH:12][CH:13]=1)=[O:18]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24820286tert-Butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylateHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

Product 1

HCID 131729823((R)-2-Hydroxymethyl-piperazin-1-yl)-[5-(4-methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-methanone, hydrochlorideYield 83%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Prepared from 5-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and 4-N-Boc-2-(R)-hydroxymethyl-piperazine by the method described in Example 2 Method B. The reaction mixture was evaporated to a solid, triturated and filtered with the aid of water, then washed with a 1 N aqueous hydrochloric acid solution followed by water. The solid was air dried afford intermediate N-Boc protected product as a colorless solid (102 mg, 86%). The Boc-protected intermediate was dissolved in a 4 N solution of hydrogen chloride in 1,4,-dioxane (2 mL) and stirred for 2 hr, after which time the reaction mixture was evaporated to approximately ¼ volume and diluted with ethyl ether (4 mL). The resulting solids were filtered and air dried to afford product as a colorless solid (85 mg, 83% overall). 1H NMR (D2O) 2.17 (s, 3H), 3.26-3.46 (m, 3H), 3.60-3.80 (m, 3H), 4.00-4.04 (m, 1H), 4.48 (dd, J=12.7, 5.3, 1H), 4.60 (obs dd, J=13.2, 3.5, 1H), 7.46 (d, J=4.3, 1H), 7.82 (d, J=4.0, 1H). 19F NMR −63.5. LC/MS 3.89 min, [M+1]+ 376.

Workup

  1. customThe reaction mixture was evaporated to a solid
  2. customtriturated
  3. filtrationfiltered with the aid of water
  4. washwashed with a 1 N aqueous hydrochloric acid solution
  5. customdried
  6. customafford intermediate N-Boc protected product as a colorless solid (102 mg, 86%)
  7. customafter which time the reaction mixture was evaporated to approximately ¼ volume
  8. additiondiluted with ethyl ether (4 mL)
  9. filtrationThe resulting solids were filtered
  10. customair dried

Sources & evidence

ORD record
ord-b1a0dbf945c34785b79f8685921b3601
Source dataset
uspto-grants-2015_05
Patent number
US09029397B2

Linked notes

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