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

HRID 1913041Notes

Reaction equation

HRID 1913041 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([O:18][C@H:19]1[C@H:24]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@@H:23]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C@@:22]([C:43]2[CH:48]=[CH:47][C:46]([Cl:49])=[C:45]([CH2:50][C:51]3[CH:56]=[CH:55][C:54]([O:57][C:58]([F:61])([F:60])[F:59])=[CH:53][CH:52]=3)[CH:44]=2)([O:41][CH3:42])[O:21][C@@H:20]1[CH2:62][OH:63])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl>[CH2:11]([O:18][C@H:19]1[C@H:24]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@@H:23]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C@@:22]([C:43]2[CH:48]=[CH:47][C:46]([Cl:49])=[C:45]([CH2:50][C:51]3[CH:52]=[CH:53][C:54]([O:57][C:58]([F:60])([F:61])[F:59])=[CH:55][CH:56]=3)[CH:44]=2)([O:41][CH3:42])[O:21][C@@H:20]1[CH:62]=[O:63])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 86685140[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methanol

Product 1

HCID 86685141(2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehydeYield 99.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

Oxalyl chloride (0.21 mL, 2.45 mmol) was dissolved in 5 mL dichloromethane and cooled to −78° C. The mixture was stirred for 15 minutes after 5 mL solution of dimethyl sulfoxide (0.24 mL, 3.26 mmol) in dichloromethane were added. Then 10 mL solution of [(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methanol 6m (1.22 g, 1.63 mmol) in dichloromethane were added before the mixture was stirred for 40 minutes. Then the reaction mixture was warmed and stirred for 1.5 hours at room temperature after triethylamine (1.18 mL, 8.15 mmol) was added and partitioned after 10 mL 1 M hydrochloric acid were added. The organic extract was washed with saturated sodium chloride solution (10 mL×2) and combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde 6n (1.21 g, yellow grease), which was used directly in the next step without purification.

Workup

  1. additionwere added
  2. temperatureThen the reaction mixture was warmed
  3. additionwas added
  4. custompartitioned after 10 mL 1 M hydrochloric acid
  5. additionwere added
  6. extractionThe organic extract
  7. washwas washed with saturated sodium chloride solution (10 mL×2)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b543864909d242b2afb2d67cf331302b
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

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