Acetic Acid → (S)-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl) 2-(7-bromo-1-hydroxy-3-methylnaphthalen-2-yl)-2-hydroxyacetate

HRID 926161

Reaction equation

HRID 926161 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([CH3:13])[CH:8]=[C:9]2[OH:12])=[CH:4][CH:3]=1.O.[C:15]([O:19][CH:20]1[CH:25]([CH:26]([CH3:28])[CH3:27])[CH2:24][CH2:23][C@@H:22]([CH3:29])[CH2:21]1)(=[O:18])[CH:16]=[O:17].C(O)(=O)C.C(#N)C>ClCCl.[Ti](Cl)(Cl)(Cl)Cl.O>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([CH3:13])[C:8]([C@H:16]([OH:17])[C:15]([O:19][C@@H:20]3[CH2:21][C@H:22]([CH3:29])[CH2:23][CH2:24][C@H:25]3[CH:26]([CH3:28])[CH3:27])=[O:18])=[C:9]2[OH:12])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 6342AcetonitrileHCID 44593838(1R)-(-)-Menthyl glyoxylate hydrateHCID 671262827-Bromo-3-methylnaphthalen-1-ol

Product 1

HCID 118023859(S)-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl) 2-(7-bromo-1-hydroxy-3-methylnaphthalen-2-yl)-2-hydroxyacetate

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

To a solution of 7-bromo-3-methylnaphthalen-1-ol (11.8 g, 50.0 mmol) in dichloromethane (25 mL) at −40° C. was added a 1 M titanium(IV) chloride solution in dichloromethane (50.0 mL, 50.0 mmol) and stirred for 20 min. (1R)-(−)-Menthyl glyoxylate hydrate (12.1 g, 52.5 mmol) was added over 15 minutes in small portions as a solid and stirred for 1 hour at 40° C. Then acetic acid (20 mL) and acetonitrile (60 mL) were added while cold. Water (200 mL) was added and the resulting solution was stirred at room temperature for 30 min. The layers were separated, and the aqueous layer was extracted with CH2Cl2. The combined organic layer was dried, filtered, concentrated. The crude material, which was about 8:1 d.r., was taken on without further purification.

Workup

  1. additionwas added over 15 minutes in small portions as a solid
  2. stirringthe resulting solution was stirred at room temperature for 30 min
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2
  5. customThe combined organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custom1 d
  9. custom, was taken on without further purification

Sources & evidence

ORD record
ord-a3138a8544fd4d748c06521b08de24f7
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Linked notes

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