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

HRID 1055573Notes

Reaction equation

HRID 1055573 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][CH3:48])=[C:43]([F:49])[C:42]=3[F:50])[CH:34]=2)([O:31][CH3:32])[O:11][C@@H:10]1[CH:51]=[O:52])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N12CCCN=C1CCCCC2.C=O.[C:66](OCC)(=[O:68])C>CN(C)C=O>[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:26]=[CH:27][CH:28]=[CH:29][CH:30]=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][CH3:48])=[C:43]([F:49])[C:42]=3[F:50])[CH:34]=2)([O:31][CH3:32])[O:11][C@@:10]1([CH2:66][OH:68])[CH:51]=[O:52])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 8857Ethyl AcetateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86685112(2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde

Product 1

HCID 118377880(2R,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehydeYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde 21l (0.52 g, 0.68 mmol) in N,N-dimethyl formamide (20 mL) were added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.05 mL, 0.34 mmol) and formaldehyde (0.83 mL, 10.28 mmol, 37 wt % solution) in turn at room temperature. The mixture was stirred at room temperature for 16 hours, and then ethyl acetate (50 mL) was added. The resulting mixture was washed with water (60 mL×5), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound 21m as yellow oil (0.52 g, 100%). This material was not further purified.

Workup

  1. washThe resulting mixture was washed with water (60 mL×5)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-2ac3b9abfc6b4dac9e84310d5cecab5b
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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