Hydrochloric Acid → (2R,3R,4S,5S)-N-heptyl-3-hydroxy-4-methoxy-5methyltetrahydro-2H-pyran-2-carboxamide

HRID 863169Notes

Reaction equation

HRID 863169 reaction equation
C([O:8][C@@H:9]1[C@@H:14]([O:15][CH3:16])[C@@H:13]([CH3:17])[CH2:12][O:11][C@H:10]1[C:18]([O:20]C)=O)C1C=CC=CC=1.[CH2:22]([NH2:29])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].Cl>>[CH2:22]([NH:29][C:18]([C@H:10]1[C@H:9]([OH:8])[C@@H:14]([O:15][CH3:16])[C@@H:13]([CH3:17])[CH2:12][O:11]1)=[O:20])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 81271-HeptanamineHCID 57058836methyl (2R,3R,4S,5S)-3-benzyloxy-4-methoxy-5-methyltetrahydro-2H-pyran-2-carboxylate

Product 1

HCID 57105024(2R,3R,4S,5S)-N-heptyl-3-hydroxy-4-methoxy-5methyltetrahydro-2H-pyran-2-carboxamideYield 50%

Conditions

Temperature
90 °C

Procedure

A mixture of methyl (2R,3R,4S,5S)-3-benzyloxy-4-methoxy-5-methyltetrahydro-2H-pyran-2-carboxylate (7 mg, 0.024 mmole) and heptylamine (0.1 ml, 0.68 mmole) was heated at 90° C. for 3 hr. The reaction mixture was adjusted to pH 3 with 0.1N aqueous HCl, and partitioned between ether (10 ml) and water (10 ml). The ether layer was dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure. A solution of the resulting crude amide in MeOH (5 ml) was stirred under hydrogen atmosphere in the presence of Pd-black (5 mg) at room temperature for 12 hr. The catalyst was removed by filtration and washed with methanol (2 ml×2). The combined filtrate and washings were evaporated to dryness under reduced pressure. The residue was chromatographed on silica gel using AcOEt/n-hexane (4:6) as an eluent to give (2R,3R,4S,5S)-N-heptyl-3-hydroxy-4-methoxy-5methyltetrahydro-2H-pyran-2-carboxamide (3.4 mg, 50% yield) as an oil; FAB-MS: m/z 288 (MH+). 1H-NMR (CDCl3)d: 0.91 (3H,t,J=6.5 Hz), 1.05 (3H,d,J=7 Hz), 1.25 (10H,br.s), 2.2 (1H, m), 3.10-3.6 (7H,br.m), 3.3 (3H,s), 3.81 (1H,dd,J=2.5 & 12 Hz), 8.0 (1H,br.s).

Workup

  1. custompartitioned between ether (10 ml) and water (10 ml)
  2. dry with materialThe ether layer was dried over anhydrous magnesium sulfate
  3. customevaporated to dryness under reduced pressure
  4. customThe catalyst was removed by filtration
  5. washwashed with methanol (2 ml×2)
  6. customThe combined filtrate and washings were evaporated to dryness under reduced pressure
  7. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-27ce22c3c0e842d8b5487b8e8646fad5
Source dataset
uspto-grants-1998_02
Patent number
US05719291

Reaction notes

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