Tetrahydrofuran → HCID 25211286, compound

HRID 1409811Notes

Reaction equation

HRID 1409811 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].Cl.[OH:20][C@@H:21]1[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]1.C1COCC1.N1CCCCC1>C(N(CC)CC)C>[OH:20][C@@H:21]1[CH2:26][CH2:25][CH2:24][N:23]([C:16]([C:14]2[S:15][C:11]([C:3]3[C:2]([CH3:1])=[C:6]([C:7]([F:8])([F:9])[F:10])[O:5][N:4]=3)=[CH:12][CH:13]=2)=[O:18])[CH2:22]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8082PiperidineHCID 2759333(3R)-piperidin-3-ol hydrochlorideHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

Product 1

HCID 25211286HCID 25211286, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Prepared from 5-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and (R)-(+)-3-hydroxypiperidine hydrochloride by the method described in Example 2 Method B reversing the order of addition such that solid acid chloride was added to a THF solution of triethylamine (containing and additional 1.1 eq. to neutralize the piperidinyl hydrochloride salt) and piperidine derivative. The reaction mixture was evaporated to an oil and partitioned between EtOAc (5 mL) and water (5 mL). The organic fraction was further washed with brine (2×5 mL), dried over MgSO4, filtered, and evaporated to an oil. The crude product was then chromatographed on silica gel with EtOAc/hexanes (50 then 75 then 100%) as eluant to afford product as a colorless solid (41 mg, 45%). 1H NMR (CDCl3) 1.56-1.62 (m, 1 H), 1.62-1.80 (m, 1 H), 1.83-2.10 (m, 2 H), 2.36 (d, J=1.3, 3 H), 2.86 (br, 1 H), 3.50-3.76 (m, 4 H), 3.82-3.98 (m, 2 H), 7.39 (br d, J=4.0, 1 H), 7.44 (d, J=4.0, 1 H). 13C NMR 7.9, 22.6, 32.5, ˜48 (br), ˜52 (br), 66.2, 114.7, 118.7 (q, J=271), 128.0, 129.6, 131.3, 140.1, 155.2 (q, J=40), 157.9, 163.5. 19F NMR −63.2. LC/MS 5.65 min, [M+1]+ 361.

Workup

  1. additioncontaining
  2. customThe reaction mixture was evaporated to an oil
  3. custompartitioned between EtOAc (5 mL) and water (5 mL)
  4. washThe organic fraction was further washed with brine (2×5 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated to an oil
  8. customThe crude product was then chromatographed on silica gel with EtOAc/hexanes (50

Sources & evidence

ORD record
ord-d1e03896830f4f1d9aead0a59807dd8d
Source dataset
uspto-grants-2014_12
Patent number
US08921399B2

Reaction notes

Loading…