Pyridine → (2'S,3'R,4'S,5'R,6'R)-3',4',5'-tris(benzyloxy)-6'-(benzyloxymethyl)-8-chloro-7-(4-ethylbenzyl)-3,3',4,4',5',6'-hexahydro-2H-spiro[benzo[b]oxepine-5,2'-pyran]

HRID 1713600Notes

Reaction equation

HRID 1713600 reaction equation
[Cl:1][C:2]1[C:3]([CH2:52][C:53]2[CH:58]=[CH:57][C:56]([CH2:59][CH3:60])=[CH:55][CH:54]=2)=[CH:4][C:5]([C@@:9]2([CH2:48][CH2:49][CH2:50][OH:51])[C@H:14]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C@@H:13]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C@H:12]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C@@H:11]([CH2:39][O:40][CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[O:10]2)=[C:6](O)[CH:7]=1.N1C=CC=CC=1.CS(OS(C)(=O)=O)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.CN(C=O)C>[CH2:16]([O:15][C@@H:14]1[C@@H:13]([O:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C@H:12]([O:31][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[C@@H:11]([CH2:39][O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[O:10][C@@:9]21[CH2:48][CH2:49][CH2:50][O:51][C:6]1[CH:7]=[C:2]([Cl:1])[C:3]([CH2:52][C:53]3[CH:58]=[CH:57][C:56]([CH2:59][CH3:60])=[CH:55][CH:54]=3)=[CH:4][C:5]2=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 11430Potassium CarbonateHCID 81560Methanesulfonic anhydrideHCID 687917355-chloro-4-(4-ethylbenzyl)-2-((2S,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-2-(3-hydroxypropyl)tetrahydro-2H-pyran-2-yl)phenol2×

Product 1

HCID 68793037(2'S,3'R,4'S,5'R,6'R)-3',4',5'-tris(benzyloxy)-6'-(benzyloxymethyl)-8-chloro-7-(4-ethylbenzyl)-3,3',4,4',5',6'-hexahydro-2H-spiro[benzo[b]oxepine-5,2'-pyran]Yield 55.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 35 (115 mg, 0.139 mmol) and pyridine (100 μL) in DCM (1 mL) was added methanesulfonic anhydride (44 mg, 0.25 mmol, 1.8 equiv). The resulting mixture was stirred at ambient temperature for 1 hour. LC/MS analysis indicated complete conversion of 35 to mono mesic ester 36. The reaction mixture was partitioned between 10% sodium bicarbonate and DCM, after which the organic phase was dried over anhydrous sodium sulfate, filtered, and evaporated to obtain a residue which was heated in DMF (3 mL) containing potassium carbonate (100 mg) at 90° C. for 0.5 hours. The resulting mixture was extracted with DCM, after which the organic layer was separated, dried (Na2SO4), filtered, and evaporated. Preparatory TLC of the residue eluting with 12% ethyl acetate in petroleum ether gave 37 (62 mg, 55% yield). 1H NMR (300 MHz, CDCl3) δ 7.54 (s, 1H), 7.16-7.28 (m, 21H), 7.08-7.11 (m, 2H), 6.98 (m, 4H), 6.97 (s, 1H), 4.81 (d, J=11.1 Hz, 1H), 4.77 (d, J=10.8 Hz, 1H), 4.73 (d, J=10.8 Hz, 1H), 4.47-4.60 (m, 3H), 4.35 (d, J=10.5 Hz, 1H), 4.16-4.24 (m, 1H), 3.70-4.02 (m, 11H), 2.60-2.71 (m, 1H), 2.54 (q, J=7.5 Hz, 2H), 2.02-2.13 (m, 1H), 1.81-1.93 (m, 2H), 1.16 (t, J=7.5 Hz, 3H). LC/MS m/z 832 (M+Na), 810 (M+H).

Workup

  1. customThe reaction mixture was partitioned between 10% sodium bicarbonate and DCM
  2. dry with materialafter which the organic phase was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customto obtain a residue which
  6. extractionThe resulting mixture was extracted with DCM
  7. customafter which the organic layer was separated
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated
  11. washPreparatory TLC of the residue eluting with 12% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-16c618a19b44473ca2ac01aed75b6a55
Source dataset
uspto-grants-2010_09
Patent number
US07795228B2

Reaction notes

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