HCID 10241002, compound → HCID 25212113, compound

HRID 1409849Notes

Reaction equation

HRID 1409849 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[S:12][C:11]([C:13]([OH:15])=O)=[CH:10][CH:9]=2)[C:4]=1[CH3:16].[NH:19]1[CH2:24][CH2:23][C@H:22]([OH:25])[C@H:21]([OH:26])[CH2:20]1.C1COCC1.CN(C=O)C>C(N(CC)CC)C>[CH3:16][C:4]1[C:5]([C:8]2[S:12][C:11]([C:13]([N:19]3[CH2:24][CH2:23][C@H:22]([OH:25])[C@H:21]([OH:26])[CH2:20]3)=[O:15])=[CH:10][CH:9]=2)=[N:6][O:7][C:3]=1[C:2]([F:1])([F:18])[F:17]

Participants

5

Reactant 3

HCID 10241002HCID 10241002, compound2×HCID 21974620tetrahydrofuran N,N-dimethylformamideHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

Product 1

HCID 25212113HCID 25212113, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Prepared from 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and (3R,4S)-3,4-Piperidinediol (CAS [135501-61-0]) by the method described in Example 2 Method B reversing the order of addition such that solid acid chloride was added to a THF/DMF (4 mL/1 mL) solution of triethylamine and (3R,4S)-3,4-Piperidinediol (2 mmol). After 30 min the reaction mixture was quenched with the addition of water. The resulting solids were then filtered and washed with a 1 N aqueous HCl solution followed by water. The material was air dried to afford product as a colorless solid (304 mg, 81%). 1H NMR (DMSO-d6) 1.53-1.60 (m, 1 H), 1.65-1.71 (m, 1 H), 2.34 (d, J=1.3, 3 H), 3.10-4.00 (br m, 6 H), 4.70 (d, J=4.4, 1 H), 4.81 (d, J=4.0, 1 H), 7.54 (br s, 1 H), 7.65 (d, J=4.0, 1 H). 19F NMR −62.2. LC/MS 5.44 min, [M+1]+ 377.

Workup

  1. customAfter 30 min the reaction mixture was quenched with the addition of water
  2. filtrationThe resulting solids were then filtered
  3. washwashed with a 1 N aqueous HCl solution
  4. customdried

Sources & evidence

ORD record
ord-c111c029ec394140b96be839b535bf0c
Source dataset
uspto-grants-2014_12
Patent number
US08921399B2

Reaction notes

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