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

HRID 1055514Notes

Reaction equation

HRID 1055514 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][CH3:49])=[CH:43][CH:42]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C@@H:10]1[CH:50]=[O:51])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N12CCCN=C1CCCCC2.[CH2:63]=[O:64]>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][CH3:49])=[CH:45][CH:46]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C@@:10]1([CH2:63][OH:64])[CH:50]=[O:51])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 117772519HCID 117772519, compound

Product 1

HCID 118377812(2R,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehydeYield 65.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde 1h (0.82 g, 1.16 mmol, obtained from the synthetic method described in step 7 of example 1) in N,N-dimethylformamide (20 mL) were added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.02 mL, 0.12 mmol) and formaldehyde (1.7 mL, 23.2 mmol, 37% in water) in turn. The mixture was stirred at room temperature for 5 hours and quenched with 10 mL of saturated aqueous sodium bicarbonate. The resulting mixture was filtered. The filtrate was extracted with ethyl acetate (20 mL×1 and 10 mL×3). The combined organic layers were washed with water (10 mL×3) and then saturated aqueous sodium chloride (10 mL×3), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=5/1 to give the title compound 8a as yellow oil (0.56 g, 65.1%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, DMSO-d6) δ(ppm): 9.99 (s, 1H), 7.55-7.49 (m, 2H), 7.43 (d, 1H), 7.34-7.24 (m, 13H), 7.07 (dd, 2H), 6.95 (d, 2H), 6.72 (d, 2H), 5.38 (dd, 1H), 4.84 (m, 3H), 4.72 (d, 1H), 4.56-4.43 (m, 2H), 4.16 (d, 1H), 4.01 (d, 1H), 3.92 (q, 2H), 3.81 (m, 3H), 3.57 (dd, 1H), 3.25 (d, 1H), 2.70 (s, 3H), 1.27 (t, 3H).

Workup

  1. customquenched with 10 mL of saturated aqueous sodium bicarbonate
  2. filtrationThe resulting mixture was filtered
  3. extractionThe filtrate was extracted with ethyl acetate (20 mL×1 and 10 mL×3)
  4. washThe combined organic layers were washed with water (10 mL×3)
  5. dry with materialsaturated aqueous sodium chloride (10 mL×3), dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluted with PE/EtOAc(v/v)=5/1

Sources & evidence

ORD record
ord-50de8d4bfa404135a071d2002911e341
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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