Hydrochloric Acid → HCID 86737782, compound

HRID 1680248Notes

Reaction equation

HRID 1680248 reaction equation
[CH3:1][C@H:2]1[C@H:15]([CH3:16])[C@@H:14]2[C@:5]3([CH2:19][CH2:18][NH:17][C@@H:13]2[CH2:12][C:11]2[CH:10]=[CH:9][C:8]([O:20][CH3:21])=[C:7]([OH:22])[C:6]3=2)[CH2:4][C:3]1=[O:23].C([O-])(O)=O.[Na+].[CH:29]1([CH2:32]Br)[CH2:31][CH2:30]1.[ClH:34]>CN(C=O)C.C(O)C>[ClH:34].[CH:29]1([CH2:32][N:17]2[CH2:18][CH2:19][C@@:5]34[C:6]5[C:7]([OH:22])=[C:8]([O:20][CH3:21])[CH:9]=[CH:10][C:11]=5[CH2:12][C@@H:13]2[C@@H:14]3[C@@H:15]([CH3:16])[C@H:2]([CH3:1])[C:3](=[O:23])[CH2:4]4)[CH2:31][CH2:30]1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 81503BromomethylcyclopropaneHCID 516892Sodium BicarbonateHCID 53858953HCID 53858953, compound

Product 1

HCID 86737782HCID 86737782, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 18b (7.20 g, 22.8 mmole), NaHCO3 (3.84 g, 45.7 mmole) and cyclopropylmethyl bromide (3.70 g, 27.4 mmole) in DMF (100 ml) was heated at 100° under argon for 2.5 hours. The mixture was processed as described for 19a-CPM to give 8.31 g (99%) of 19b-CPM as a foam. NMR: δ 6.90 (aromatic); 6.35, broad s, 1H (hydroxyl proton); 4.23 (H-5α); 3.78 (CH3O--); 1.10, unsymmetrical d, (8β-CH3, J=5 Hz); 0.92 symmetrical d, (7α-CH3, J=6 Hz). The foam was converted to the HCl salt by dissolving the free base in ethanol, adding an excess of concentrated HCl followed by evaporation to dryness. The residue was azeotroped with 1:1 ethanol-toluene, then toluene and finally crystallized from acetone to give 8.24 g (90%) of 19b-CPM.HCl, mp 194°-195°. Recrystallization from acetone gave an analytical sample of 19b-CPM.HCl as the hemi-acetone solvate. The presence of acetone was confirmed by the nmr of 19b-CMP.HCl taken in DMSO-d6.

Workup

  1. temperaturewas heated at 100° under argon for 2.5 hours
  2. customto give 8.31 g (99%) of 19b-CPM as a foam
  3. customfollowed by evaporation to dryness
  4. customThe residue was azeotroped with 1:1 ethanol-toluene
  5. customtoluene and finally crystallized from acetone

Sources & evidence

ORD record
ord-569a33e56f224e2196c10044c6cbde17
Source dataset
uspto-grants-1981_06
Patent number
US04272541

Reaction notes

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