Triethylamine → tert-Butyl [(2S,4S)-4-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-5-methyl-1-oxohexan-2-yl]carbamate

HRID 2258295Notes

Reaction equation

HRID 2258295 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13]([NH:15][C@@H:16]([CH2:19][C@H:20]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[C:27]([O:33][CH2:34][CH2:35][CH2:36][O:37][CH3:38])[CH:26]=1)[CH:21]([CH3:23])[CH3:22])[CH2:17][OH:18])=[O:14])([CH3:11])([CH3:10])[CH3:9]>S(OC)(OC)(=O)=O.ClCCl>[C:8]([O:12][C:13]([NH:15][C@@H:16]([CH2:19][C@H:20]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[C:27]([O:33][CH2:34][CH2:35][CH2:36][O:37][CH3:38])[CH:26]=1)[CH:21]([CH3:23])[CH3:22])[CH:17]=[O:18])=[O:14])([CH3:11])([CH3:10])[CH3:9]

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 11495886HCID 11495886, compound

Product 1

HCID 11590225tert-Butyl [(2S,4S)-4-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-5-methyl-1-oxohexan-2-yl]carbamate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6497Dimethyl SulfateSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., first triethylamine (175.6 ml) and then a solution of pyridine/sulfur trioxide complex (221 g) in dimethyl sulfate (0.84 liters) are added dropwise over a period of 45 minutes, with stirring, to a solution of 2(S)-(tert-butoxycarbonyl)amino-4(S)-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-5-methyl-hexanol (184.8 g) in dichloromethane (1.34 liters). When the addition is complete, the batch is stirred for a further 30 minutes at 0° C. and then ice-water (1.6 liters) is added. The mixture is extracted with dichloromethane (3×1.6 liters), and the combined organic phases are washed with saturated sodium hydrogen carbonate solution (2×1.6 liters), water (1.6 liters) and saturated sodium chloride solution and filtered through cotton wool and the solvent is removed in vacuo. The residue is dried under a high vacuum, yielding the crude title compound in the form of an oil (190 g): Rf (ethyl acetate/hexane 1:1)=0.44. IR (CH2Cl2) 3430, 2960, 1710, 1589, 1515 cm-. 1H-NMR (CDCl3): δ 0.86 (m, 6H), 1.44 (s, 9H), 1.55-1.8 (m, 4H), 2.09 (m, 2H), 2.4-2.7 (m, 2H), 3.35 (s, 3H), 3.57 (t, J=6.4 Hz, 2H), 3.83 (s, 3H), 4.10 (t, J=6.4 Hz, 2H), 4.05-4.20 (m, 1H), 4.89 (d, br., 1), 6.7-6.8 (m, 3H), 9.50 (s, 1H).

Workup

  1. additionWhen the addition
  2. extractionThe mixture is extracted with dichloromethane (3×1.6 liters)
  3. washthe combined organic phases are washed with saturated sodium hydrogen carbonate solution (2×1.6 liters), water (1.6 liters) and saturated sodium chloride solution
  4. filtrationfiltered through cotton wool
  5. customthe solvent is removed in vacuo
  6. customThe residue is dried under a high vacuum

Sources & evidence

ORD record
ord-376fee5c0f7b4878895068cd2394588a
Source dataset
uspto-grants-1997_08
Patent number
US05659065

Reaction notes

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