Hydrochloric Acid → HCID 86616401, compound

HRID 1866692Notes

Reaction equation

HRID 1866692 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]1[CH:20]=[C:19]([F:21])[CH:18]=[C:17]2[C:13]=1[CH2:14][CH2:15][C:16]2([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:22][OH:23].C(N(CC)C(C)C)(C)C.Cl>C(Cl)Cl>[F:11][C:12]1[CH:20]=[C:19]([F:21])[CH:18]=[C:17]2[C:13]=1[CH2:14][CH2:15][C:16]2([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])[CH:22]=[O:23]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 86616400HCID 86616400, compound

Product 1

HCID 86616401HCID 86616401, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-60 °C

Procedure

To a stirred solution of oxalyl chloride (0.91 mL, 10.4 mmol) in CH2Cl2 (40 mL) at −78° C. was added DMSO (1.48 mL, 20.9 mmol), dropwise, over 5 min. The reaction mixture was stirred for 30 min, during which time it warmed to −60° C., then a solution of tert-butyl [4,6-difluoro-1-(hydroxymethyl)-2,3-dihydro-1H-inden-1-yl]carbamate from Step E (2.08 g, 6.95 mmol) in CH2Cl2 (22 mL) was added, dropwise, over 30 min. During the addition, the reaction temperature rose to −45° C. and it was stirred at this temperature for an additional 15 min. To the resulting mixture was added N,N-diisopropylethylamine (7.28 mL, 41.7 mmol), dropwise, over 2 min. The mixture was allowed to warm to 0° C., stirred for 15 min then poured into ice (60 mL) and 1 N aqueous HCl (30 mL). The resulting mixture was extracted with CH2Cl2 (2×100 mL). The combined organic extracts were washed with H2O (30 mL), then brine (50 mL), then dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: m/z=224 (M−OC4H9).

Workup

  1. waitdropwise, over 30 min
  2. additionDuring the addition
  3. customrose to −45° C.
  4. stirringit was stirred at this temperature for an additional 15 min
  5. waitdropwise, over 2 min
  6. temperatureto warm to 0° C.
  7. stirringstirred for 15 min
  8. extractionThe resulting mixture was extracted with CH2Cl2 (2×100 mL)
  9. washThe combined organic extracts were washed with H2O (30 mL)
  10. dry with materialbrine (50 mL), then dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bc7031227f6c435899627b7905f25ac7
Source dataset
uspto-grants-2009_12
Patent number
US07629338B2

Reaction notes

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