Dimethylformamide → HCID 178495936, compound

HRID 2095748Notes

Reaction equation

HRID 2095748 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C:8]([OH:10])=O)[CH2:4][CH2:3]1.[CH3:11][O:12][CH:13]([O:17][CH3:18])[CH2:14][NH:15][CH3:16].O.ON1C2C=CC=CC=2N=N1.CN(C=O)C>>[CH3:11][O:12][CH:13]([O:17][CH3:18])[CH2:14][N:15]([CH3:16])[C:8]([C@H:5]1[CH2:4][CH2:3][C@H:2]([OH:1])[CH2:7][CH2:6]1)=[O:10]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 85032,2-DimethoxyethylmethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 178525780HCID 178525780, compound

Product 1

HCID 178495936HCID 178495936, compound

Procedure

To a solution of trans-4-hydroxycyclohexanecarboxylic acid (1.00 g, 6.94 mmol), 2,2-dimethoxy-N-methylethanamine (0.909 g, 7.63 mmol), and 1-Hydroxybenzotriazole hydrate (1.17 g, 7.63 mmol) in DMF (25 mL, 320 mmol) was added N-(3-Dimethylaminopropyl)-W-ethylcarbodiimide hydrochloride (1.46 g, 7.63 mmol) at ambient temperature, and the solution was stirred at ambient temperature overnight. Most of the DMF was evaporated in vacuo, and the residue was partitioned between water and EtOAc. The layers were separated, and the aqueous layer was extracted with EtOAc (4×25 mL), saturated with NaCl, and extracted again with EtOAc (5×25 mL). The combined EtOAc extracts were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound as yellow oil that was used without further purification in the next step. 1H NMR (400 MHz, CDCl3): δ=4.48 (t, J=5.4 Hz, 1H, major rotamer), 4.39 (t, J=5.4 Hz, 1H, minor rotamer), 3.70-3.61 (m, 1H), 3.45-3.42 (m, 2H), 3.43 (s, 6H, minor rotamer), 3.40 (s, 6H, major rotamer), 3.11 (s, 3H, major rotamer), 2.97 (s, 3H, minor rotamer), 2.56 (tt, J=11.6, 3.8 Hz, 1H, minor rotamer), 2.46 (tt, J=11.8, 3.4 Hz, 1H, major rotamer), 2.11-2.00 (m, 2H), 1.86-1.74 (m, 2H), 1.71-1.55 (m, 3H), 1.36-1.23 (m, 2H). MS (ES+): m/z=268.11 (87) [MNa+], 246.15 (42) [MH+], 214.13 (100) [MH+−MeOH]. HPLC: tR=2.36 min (polar—5 min, ZQ3).

Workup

  1. customMost of the DMF was evaporated in vacuo
  2. customthe residue was partitioned between water and EtOAc
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (4×25 mL), saturated with NaCl
  5. extractionextracted again with EtOAc (5×25 mL)
  6. washThe combined EtOAc extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ea87d4261a3f4733b7d443b798287b46
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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