Formaldehyde → (2R,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehyde

HRID 1055601Notes

Reaction equation

HRID 1055601 reaction equation
[CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@:12]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH2:48][C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)=[CH:43][CH:42]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C@@H:10]1[CH:55]=[O:56])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:57]=[O:58].N12CCCN=C1CCCCC2>CN(C)C=O>[CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@:12]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]3[CH:42]=[CH:43][C:44]([O:47][CH2:48][C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)=[CH:45][CH:46]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C@@:10]1([CH2:57][OH:58])[CH:55]=[O:56])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 131736397HCID 131736397, compound

Product 1

HCID 131736398(2R,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehydeYield 100.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde 25i (1.0 g, 1.3 mmol) in N,N-dimethyl formamide (20 mL) was added formaldehyde (2.6 mL, 32.5 mmol, 37 wt % solution) at room temperature, and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.3 mL, 0.78 mmol) was added to adjust the pH to 9. The mixture was stirred at room temperature for 16 hours and extracted with ethyl acetate (50 mL×2). The combined organic layers were washed with water (30 mL×2) and saturated aqueous sodium chloride (30 mL×2) in turn, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound 25j as yellow oil (1.04 g, 100%). This material was not further purified.

Workup

  1. extractionextracted with ethyl acetate (50 mL×2)
  2. washThe combined organic layers were washed with water (30 mL×2) and saturated aqueous sodium chloride (30 mL×2) in turn
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-8e161284ee834df08afdca0d3393f41a
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

Loading…