Morpholine → HCID 59837372, compound

HRID 273052Notes

Reaction equation

HRID 273052 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.[N:26]1([CH2:32][CH2:33][CH2:34][O:35][C:36]2[CH:41]=[CH:40][C:39]([C:42]3([C:48]([OH:50])=O)[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[CH:38][CH:37]=2)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.[NH:51]1[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1.CCN(C(C)C)C(C)C>CN(C)C=O>[N:51]1([C:48]([C:42]2([C:39]3[CH:40]=[CH:41][C:36]([O:35][CH2:34][CH2:33][CH2:32][N:26]4[CH2:27][CH2:28][O:29][CH2:30][CH2:31]4)=[CH:37][CH:38]=3)[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[O:50])[CH2:56][CH2:55][O:54][CH2:53][CH2:52]1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68577604HCID 68577604, compound

Product 1

HCID 59837372HCID 59837372, compoundYield 108.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (200 mg, 0.5 mmol) was added to a solution of 4-[4-(3-Morpholin-4-yl-propoxy)-phenyl]-tetrahydro-pyran-4-carboxylic acid hydrochloride (160 mg, 0.4 mmol), morpholine (54 μL, 0.6 mmol) and Hunig's base (180 μL, 1 mmol) in N,N-dimethylformamide (2 mL). The mixture was stirred at room temperature for 3 hours and then concentrated in vacuo. The residue was partitioned between 2M NaOH solution (20 mL) and DCM (2×20 mL). The organics were combined, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 to 90:10:1, by volume) to provide the title compound (182 mg, 100%) as a pale brown solid. 1H NMR (400 MHz, CDCl3) δ 1.93-2.04 (m, 4H), 2.20 (m, 2H), 2.42-2.55 (m, 6H), 3.22-3.43 (br m, 8H), 3.72 (t, 4H), 3.79 (m, 2H), 3.90 (m, 2H), 4.00 (t, 2H), 6.88 (d, 2H), 7.17 (d, 2H). LRMS APCI+ m/z 419 [MH]+.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between 2M NaOH solution (20 mL) and DCM (2×20 mL)
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 to 90:10:1, by volume)

Sources & evidence

ORD record
ord-fbc55436151d4f6d9b011406ebd8d814
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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