Dimethyl Sulfoxide → benzyl (1S,2R,4aS,6aR,6aS,6bR,8aR,12aR,14bS)-1,2,6a,6b,9,9,12a-heptamethyl-10-oxo-1,2,3,4,5,6,6a,7,8,8a,11,12,13,14b-tetradecahydropicene-4a-carboxylate

HRID 2405522Notes

Reaction equation

HRID 2405522 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][C@H:12]1[CH2:33][CH2:32][C@@:31]2([CH3:34])[C@@H:14]([CH2:15][CH2:16][C@:17]3([CH3:48])[C@@H:30]2[CH2:29][CH:28]=[C:27]2[C@@:18]3([CH3:47])[CH2:19][CH2:20][C@:21]3([C:37]([O:39][CH2:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[O:38])[C@H:26]2[C@@H:25]([CH3:35])[C@H:24]([CH3:36])[CH2:23][CH2:22]3)[C:13]1([CH3:50])[CH3:49].C(N(CC)CC)C>C(Cl)Cl>[CH3:35][C@@H:25]1[C@@H:26]2[C@@:21]([C:37]([O:39][CH2:40][C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)=[O:38])([CH2:20][CH2:19][C@:18]3([CH3:47])[C:27]2=[CH:28][CH2:29][C@H:30]2[C@@:17]3([CH3:48])[CH2:16][CH2:15][C@@H:14]3[C@:31]2([CH3:34])[CH2:32][CH2:33][C:12](=[O:11])[C:13]3([CH3:49])[CH3:50])[CH2:22][CH2:23][C@H:24]1[CH3:36]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 67952979Benzyl ursolate2×

Product 1

HCID 67952365benzyl (1S,2R,4aS,6aR,6aS,6bR,8aR,12aR,14bS)-1,2,6a,6b,9,9,12a-heptamethyl-10-oxo-1,2,3,4,5,6,6a,7,8,8a,11,12,13,14b-tetradecahydropicene-4a-carboxylateYield 95.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
-50 °C

Procedure

To a solution of oxalyl chloride (2.57 mL, 5.14 mmol) in methylene chloride (5 mL) at −78° C. under nitrogen was added dropwise a solution of DMSO (0.46 mL 6.4 mmol) in methylene chloride (5 mL). The mixture was allowed to warm to −50° C. To this was added a solution of the (1S,2R,4aS,6aS,6bR,8aR,10S,12aR,12bR,14bS)-benzyl 10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4-a-carboxylate (intermediate A1) (2.34 gm, 4.28 mmol) in methylene chloride (15 mL) forming a white milky suspension. The mixture was stirred for an additional 15 minutes at −50° C. after the addition, it was then treated with triethylamine (1.79 mL, 12.84 mmol) and the reaction mixture was slowly warmed to RT. It was diluted with methylene chloride (100 mL), washed with water (2×100 mL), followed by brine (50 mL). The organic phase was separated out, dried over anhydrous sodium sulfate, and concentrated in vacuo to a syrup. This crude material was partitioned over a silica gel column, eluted with 9:1, hexanes:ethyl acetate solvent to give the title compound as a pale solid (2.22 g, 95%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.69 (s, 3H), 0.87 (d, J=6.53 Hz, 3H), 0.93-0.97 (m, 3H), 1.03 (s, 3H), 1.05 (s, 3H), 1.09 (s, 6H), 1.26-1.40 (m, 4H), 1.40-1.54 (m, 5H), 1.59 (d, J=9.03 Hz, 2H), 1.70 (br. s., 2H), 1.93 (dd, J=9.54, 3.26 Hz, 4H), 1.97-2.08 (m, 2H), 2.29 (d, J=11.04 Hz, 1H), 2.38 (ddd, J=15.94, 6.90, 3.76 Hz, 1H), 2.49-2.61 (m, 1H), 4.97-5.03 (m, 1H), 5.10-5.15 (m, 1H), 5.27 (t, J=3.51 Hz, 1H), 7.31-7.39 (m, 5H).

Workup

  1. customforming a white milky suspension
  2. additionafter the addition, it
  3. temperaturethe reaction mixture was slowly warmed to RT
  4. washwashed with water (2×100 mL)
  5. customThe organic phase was separated out
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo to a syrup
  8. customThis crude material was partitioned over a silica gel column
  9. washeluted with 9:1, hexanes

Sources & evidence

ORD record
ord-4992bda77bb9464b8921d4cdd9080d25
Source dataset
uspto-grants-2014_08
Patent number
US08802661B2

Reaction notes

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