Hydrochloric Acid → HCID 178513797, compound

HRID 869627Notes

Reaction equation

HRID 869627 reaction equation
[F:1][C:2]([F:13])([F:12])[C@@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([OH:11])=O)[CH2:5][CH2:4]1.C(Cl)(=O)C(Cl)=O.Cl.Cl.[NH:22]1[CH2:26][CH2:25][CH2:24][C@@H:23]1[CH2:27][O:28][C:29]1[C:30]([C:35]([NH2:37])=[O:36])=[N:31][CH:32]=[CH:33][CH:34]=1.C(N(CC)CC)C.Cl>ClCCl.C(OCC)(=O)C.CN(C)C=O>[F:12][C:2]([F:1])([F:13])[C@@H:3]1[CH2:4][CH2:5][C@H:6]([C:9]([N:22]2[CH2:26][CH2:25][CH2:24][C@@H:23]2[CH2:27][O:28][C:29]2[C:30]([C:35]([NH2:37])=[O:36])=[N:31][CH:32]=[CH:33][CH:34]=2)=[O:11])[CH2:7][CH2:8]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 66960633(R)-3-(pyrrolidin-2-ylmethoxy)picolinamide dihydrochlorideHCID 178525709HCID 178525709, compound

Product 1

HCID 178513797HCID 178513797, compoundYield 58.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To an ice-cold solution of cis-4-(trifluoromethyl)cyclohexanecarboxylic acid (267 mg, 1.36 mmol) in dichloromethane (5 mL), oxalyl chloride (0.18 mL, 2.04 mmol) and several drop of N,N-dimethylformamide were added. After being stirred at room temperature for 1 h, the mixture was concentrated in vacuo to give a waxy solid. The residual solid was dissolved with dichloromethane (3 mL) and added to the mixture of (R)-3-(pyrrolidin-2-ylmethoxy)picolinamide dihydrochloride (200 mg, 0.68 mmol, EXAMPLE 1 Step 3) and triethylamine (0.48 mL, 3.40 mmol) in dichloromethane (5 mL) at 0° C. After being stirred at 0° C. for 2 h, the mixture was dissolved with ethyl acetate and 2 N hydrochloric acid. The aqueous layer was washed with ethyl acetate, and basified with aq. ammonia. The mixture was extracted with ethyl acetate twice, and washed with brine. The combined extracts were dried over sodium sulfate and concentrated in vacuo to give an amber oil. The residual oil was purified by preparative TLC (methanol/dichloromethane 1:10) to afford 160 mg of the title compound as a colorless viscous oil.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customto give a waxy solid
  3. stirringAfter being stirred at 0° C. for 2 h
  4. washThe aqueous layer was washed with ethyl acetate
  5. extractionThe mixture was extracted with ethyl acetate twice
  6. washwashed with brine
  7. dry with materialThe combined extracts were dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give an amber oil
  10. customThe residual oil was purified by preparative TLC (methanol/dichloromethane 1:10)

Sources & evidence

ORD record
ord-0ea77d66e510479e966b50e144d83c36
Source dataset
uspto-grants-2015_03
Patent number
US08969383B2

Reaction notes

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