Dimethyl Sulfoxide → HCID 86760286, compound

HRID 1245626Notes

Reaction equation

HRID 1245626 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH2:12][C@@H:13]1[C@@H:17]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[CH2:16][N:15]([CH2:25][C:26]2([C:32]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[O:33])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[CH2:14]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH:12]([C@@H:13]1[C@@H:17]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=2)[CH2:16][N:15]([CH2:25][C:26]2([C:32]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[O:33])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]2)[CH2:14]1)=[O:11]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 86760284HCID 86760284, compound

Product 1

HCID 86760286HCID 86760286, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2.1 mL (24.2 mmol) of oxalyl chloride in 110 mL of CH2Cl2 at −78° C. was treated with 2.6 mL (36.8 mmol) of DMSO maintaining the temperature at less than −60° C. The resulting mixture was stirred cold for 5 min. A solution of 4.5 g (10.5 mmol) of 1-{[(3R,4S)-3-(hydroxymethyl)-4-(3-fluorophenyl)pyrrolidin-1-yl]methyl}cyclohexanecarboxylic acid, benzyl ester (from Step B) in 10 mL of CH2Cl2 was added maintaining the temperature at less than −60° C. The resulting mixture was stirred cold for 60 min. The mixture was treated with 15 mL (84.0 mmol) of N,N-diisopropylethylamine maintaining the temperature at less than −60° C. The reaction was warmed to 0° C., stirred for 20 min and quenched with 20 mL 0.5 N KHSO4. The mixture was partitioned between 250 mL of CH2Cl2 and 100 mL of H2O and the layers were separated. The aqueous layer was extracted with 250 mL of CH2Cl2. The combined organic phases were dried over MgSO4 and concentrated. Purification by Biotage Flash 40 using a 40 M cartridge and 1.0 L each of 95:5 to 90:10 v/v hexane/ethyl acetate as the eluant afforded the title compound: 1H NMR (500 MHz, CDCl3) δ 1.24–3.48 (18H), 5.16 (ABq, J=12.2, 2H), 6.90–7.02 (3H), 7.22–7.39 (6H), 9.59 (s, 1H).

Workup

  1. temperaturemaintaining the temperature at less than −60° C
  2. stirringThe resulting mixture was stirred cold for 60 min
  3. stirringstirred for 20 min
  4. customquenched with 20 mL 0.5 N KHSO4
  5. customThe mixture was partitioned between 250 mL of CH2Cl2 and 100 mL of H2O
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with 250 mL of CH2Cl2
  8. dry with materialThe combined organic phases were dried over MgSO4
  9. concentrationconcentrated
  10. customPurification by Biotage Flash 40 using a 40 M cartridge and 1.0 L each of 95:5 to 90:10 v/v hexane/ethyl acetate as the eluant

Sources & evidence

ORD record
ord-824511d16a0a40de9d9cac64784b5620
Source dataset
uspto-grants-2006_10
Patent number
US07125887B2

Reaction notes

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