Toluene → HCID 46178372, compound

HRID 1886987Notes

Reaction equation

HRID 1886987 reaction equation
[CH3:1][N:2]([CH3:28])[CH2:3][CH2:4][N:5]1[C:11](=[O:12])[C@H:10]([OH:13])[C@H:9]([C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=2)[S:8][C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]1=2.[C:29](Cl)(=[O:31])[CH3:30].C1(C)C=CC=CC=1>N1C=CC=CC=1.C(Cl)Cl>[C:29]([O:13][C@@H:10]1[C@H:9]([C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=2)[S:8][C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([CH2:4][CH2:3][N:2]([CH3:1])[CH3:28])[C:11]1=[O:12])(=[O:31])[CH3:30]

Participants

6

Reactant 3

HCID 1140TolueneHCID 6367Acetyl chlorideHCID 67218352HCID 67218352, compound

Product 1

HCID 46178372HCID 46178372, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To 127 mg (0.317 mmol) of methyl 4-((2S,3S)-5-(2-(dimethylamino)ethyl)-3-hydroxy-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-2-yl)benzoate in 160 μL of pyridine at 0° C. was added 25 μL (0.35 mmol) of acetyl chloride. The solution was stirred at 0° C. for 2 hours. The solvent was evaporated to leave a residue which was co-evaporated with toluene (3×). The material was then dissolved in DCM, washed with 1 N NaOH, dried (Na2SO4), and evaporated. Purification was afforded by flash chromatography on silica gel, eluting first with DCM then gradually increasing to 5% methanol/DCM to give 1m. MS found M+H=443. The observed 1H NMR coupling constants between the C2 and C3 methine protons (J=7.4 Hz) confirmed retention of the cis stereochemical relationship. The hydrochloride salt of 1m was recrystallized from isopropanol/ether; mp 214-216° C.; [α]25D+98.9° (c 0.99, CHCl3).

Workup

  1. customThe solvent was evaporated
  2. customto leave a residue which
  3. washwashed with 1 N NaOH
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customPurification
  7. customwas afforded by flash chromatography on silica gel
  8. washeluting first with DCM
  9. temperaturethen gradually increasing to 5% methanol/DCM

Sources & evidence

ORD record
ord-c0afcba160e743489a3bfc493684c07c
Source dataset
uspto-grants-2013_08
Patent number
US08501727B2

Reaction notes

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