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

HRID 1055537Notes

Reaction equation

HRID 1055537 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][C:48]([F:51])([F:50])[F:49])=[CH:43][CH:42]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C@@H:10]1[CH:52]=[O:53])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.N12CCCN=C1CCCCC2.[C:67](OCC)(=[O:69])C>O1CCCC1.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: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][C:48]([F:50])([F:51])[F:49])=[CH:45][CH:46]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C@@:10]1([CH2:67][OH:69])[CH:52]=[O:53])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8857Ethyl AcetateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86685141(2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde

Product 1

HCID 118377847(2R,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy) phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehydeYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy) phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde 15l (100 mg, 0.13 mmol) in tetrahydrofuran (5 mL) were added formaldehyde (72.3 mg, 2.47 mmol, 37 wt % solution) and 1,8-diazabicyclo[5.4.0]undec-7-ene (16.3 mg, 0.11 mmol) in turn at room temperature. The mixture was stirred at room temperature for 48 hours, and then ethyl acetate (20 mL) and water (5 mL) were added. The resulting mixture was partitioned. The aqueous layer was extracted with ethyl acetate (10 mL×2). The combined organic layers were washed with saturated aqueous sodium chloride (10 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound 15m as yellow oil (108 mg, 100%). This material was not further purified.

Workup

  1. customThe resulting mixture was partitioned
  2. extractionThe aqueous layer was extracted with ethyl acetate (10 mL×2)
  3. washThe combined organic layers were washed with saturated aqueous sodium chloride (10 mL×2)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-301cb6cfdb29450390704f1099b8c962
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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