Citric Acid → HCID 178523110, compound

HRID 869654Notes

Reaction equation

HRID 869654 reaction equation
[F:1][C:2]([F:28])([F:27])[C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([N:11]2[CH2:15][CH2:14][CH2:13][C@@H:12]2[CH2:16][O:17][C:18]2[C:19]([C:24]([NH2:26])=[O:25])=[N:20][CH:21]=[CH:22][CH:23]=2)=[O:10])[CH2:5][CH2:4]1.[H-].[Na+].I[CH2:32][C:33]1([OH:39])[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN1CCCC1=O>[OH:39][C:33]1([CH2:32][NH:26][C:24](=[O:25])[C:19]2[C:18]([O:17][CH2:16][C@H:12]3[CH2:13][CH2:14][CH2:15][N:11]3[C:9]([C@H:6]3[CH2:7][CH2:8][C@H:3]([C:2]([F:1])([F:27])[F:28])[CH2:4][CH2:5]3)=[O:10])=[CH:23][CH:22]=[CH:21][N:20]=2)[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 669618924-(iodomethyl)tetrahydro-2H-pyran-4-olHCID 178513798HCID 178513798, compound

Product 1

HCID 178523110HCID 178523110, compoundYield 53.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 3-(((R)-1-(trans-4-(trifluoromethyl)cyclohexanecarbonyl)pyrrolidin-2-yl)methoxy)picolinamide (105 mg, 0.263 mmol, EXAMPLE 75 Step 1) in 1-Methyl-2-pyrrolidone (5 mL) was added sodium hydride (60% oil dispersant, 16 mg, 0.394 mmol) at ambient temperature. After being stirred at room temperature for 1 h, 4-(iodomethyl)tetrahydro-2H-pyran-4-ol (76 mg, 0.315 mmol, EXAMPLE 77 Step 1) was added to the mixture. The mixture was heated at 70° C. and stirred for 3 days. After cooling to room temperature, aq. citric acid was added to the mixture. The mixture was extracted with ethyl acetate twice and washed successively with aq. sodium thiosulfate, aq. sodium bicarbonate, and brine. The extracts were combined and dried over sodium sulfate and concentrated in vacuo to afford 72 mg of crude oil. The residual oil was purified by preparative HPLC purification.

Workup

  1. temperatureThe mixture was heated at 70° C.
  2. stirringstirred for 3 days
  3. temperatureAfter cooling to room temperature
  4. extractionThe mixture was extracted with ethyl acetate twice
  5. washwashed successively with aq. sodium thiosulfate, aq. sodium bicarbonate, and brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bb22f43862cd429d814501d972bd77a9
Source dataset
uspto-grants-2015_03
Patent number
US08969383B2

Reaction notes

Loading…