Methanol → HCID 117843761, compound

HRID 2209183Notes

Reaction equation

HRID 2209183 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]([O:19][C@@H:20]([C@H:22]2[CH2:26][N:25]([C@@H:27]([C:29]3[CH:34]=[CH:33][C:32]([O:35]C)=[CH:31][CH:30]=3)[CH3:28])[C:24](=[O:37])[CH2:23]2)[CH3:21])[C:12]2[S:16][C:15]([CH3:17])=[N:14][C:13]=2[CH:18]=1)C1C=CC=CC=1.B(Br)(Br)Br.CO.CCN(CC)CC.N(CC)CC>C(Cl)Cl>[OH:8][C:9]1[CH:10]=[C:11]([O:19][C@@H:20]([C@H:22]2[CH2:26][N:25]([C@@H:27]([C:29]3[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=3)[CH3:28])[C:24](=[O:37])[CH2:23]2)[CH3:21])[C:12]2[S:16][C:15]([CH3:17])=[N:14][C:13]=2[CH:18]=1

Participants

7

Reactant 5

HCID 887MethanolHCID 8021DiethylamineHCID 8471TriethylamineHCID 25134Boron tribromideHCID 131735980HCID 131735980, compound

Product 1

HCID 117843761HCID 117843761, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

(R)-4-((R)-1-(5-(benzyloxy)-2-methylbenzo[d]thiazol-7-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 4.03F (490 mg, 0.95 mmol) was dissolved in DCM (10 mL) under Ar. The solution was cooled to −78° C., and a 1.0 M solution of BBr3 in DCM (7.1 mL, 7.1 mmol) was added over 1 min. The resulting mixture was allowed to warm to r.t. and was stirred for an additional 45 min. The mixture was then cooled in an ice water bath, and MeOH (4.6 mL, 110 mmol) was added over 1 min. Et3N (4.1 mL, 29 mmol) and Et2NH (0.31 mL, 3.0 mmol) were then added, and the mixture was removed from the cold bath. After an additional 15 min, the mixture was concentrated, and the crude residue was dissolved in MeOH (30 mL) and concentrated. The resulting residue was partitioned between EtOAc (50 mL) and water (30 mL). The phases were separated, and the organic phase was washed with a mixture of water (25 mL), 3 M aqueous HCl (7.5 mL), and brine (25 mL). The organic phase was washed with a mixture of saturated aqueous NaHCO3 (20 mL) and brine (20 mL) and was dried over Na2SO4, filtered, and concentrated to afford crude (R)-4-((R)-1-(5-hydroxy-2-methylbenzo[d]thiazol-7-yloxy)ethyl)-1-((R)-1-(4-hydroxyphenyl)ethyl)pyrrolidin-2-one that was used without further purification.

Workup

  1. temperatureto warm to r.t.
  2. temperatureThe mixture was then cooled in an ice water bath
  3. customthe mixture was removed from the cold bath
  4. waitAfter an additional 15 min
  5. concentrationthe mixture was concentrated
  6. dissolutionthe crude residue was dissolved in MeOH (30 mL)
  7. concentrationconcentrated
  8. customThe resulting residue was partitioned between EtOAc (50 mL) and water (30 mL)
  9. customThe phases were separated
  10. washthe organic phase was washed with a mixture of water (25 mL), 3 M aqueous HCl (7.5 mL), and brine (25 mL)
  11. washThe organic phase was washed with a mixture of saturated aqueous NaHCO3 (20 mL) and brine (20 mL)
  12. dry with materialwas dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-64df9ccc17034b7698c2c52ca0c44528
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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