tert-Butyl 2-(3-(3-(3,4-dimethoxyphenyl)propanoyl)phenoxy)acetate → tert-Butyl {3-[3-(3,4-dimethoxyphenyl)-1-hydroxypropyl]phenoxy}acetate

HRID 426395Notes

Reaction equation

HRID 426395 reaction equation
[C:1]([O:5][C:6]([CH2:8][O:9][C:10]1[CH:11]=[C:12]([C:16](=[O:29])[CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=2)[CH:13]=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B(Cl)([C@@H]1[C@@H](C)[C@H]2C(C)(C)[C@@H](C2)C1)[C@@H]1[C@@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1>C1COCC1>[C:1]([O:5][C:6]([CH2:8][O:9][C:10]1[CH:11]=[C:12]([CH:16]([OH:29])[CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=2)[CH:13]=[CH:14][CH:15]=1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 2771667tert-Butyl 2-(3-(3-(3,4-dimethoxyphenyl)propanoyl)phenoxy)acetateHCID 91873398(+)-b-Chlorodiisopinocamphenylborane

Product 1

HCID 22128940tert-Butyl {3-[3-(3,4-dimethoxyphenyl)-1-hydroxypropyl]phenoxy}acetateYield 90.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1-(3-(tert-Butoxycarbonylmethoxy)phenyl)-3-(3,4-dimethoxyphenyl)propan-1-one (10) (3.0 g, 7.49 mmol) in THF (5 mL) at −20° C. was treated with a solution of (+)-B-chlorodiisopinocamphenylborane (2.9 g, 8.99 mmol) in THF (10 mL) at −20° C. The resulting mixture was allowed to stand in a −20° C. freezer for 48 h after which time the mixture was evaporated and treated with diethyl ether (25 mL) followed by diethanolamine (8 mL). The viscous mixture was allowed to stir at room temperature for 3 h, after which time, was filtered through a pad of Celite with the aid of diethyl ether. The cloudy filtrate was evaporated and flash chromatographed (silica gel, 30% 40% EtOAc/hexanes) to afford 2.72 g (90%) of a clear colorless oil. (95% ee by Chiracel HPLC, 25% i-PrOH/hexanes, retention time 44.4 min for the R-enantiomer and 35.7 min for the S-enantiomer): IR (neat) 3525, 2935, 1750, 1515, 1150 cm−1; 1H NMR (CDCl3, 300 MHz) 7.30-7.25 (m, 2H), 6.99-6.73 (m, 5H), 4.68 (m, 1H), 4.53 (s, 2H), 3.88 (s, 3H), 3.87 (s, 3H), 2.72-2.63 (m, 2H), 2.12-1.97 (m, 2H), 1.50 (s, 9H); 13C NMR (CDCl3, 75 MHz) 168.4, 158.5, 149.3, 147.6, 146.9, 134.8, 130.0, 120.6, 119.5, 114.0, 112.6, 112.2, 111.7, 82.7, 74.1, 66.1, 56.3, 56.2, 41.0, 32.0, 28.4.

Workup

  1. customafter which time the mixture was evaporated
  2. additiontreated with diethyl ether (25 mL)
  3. filtrationafter which time, was filtered through a pad of Celite with the aid of diethyl ether
  4. customThe cloudy filtrate was evaporated
  5. customflash chromatographed (silica gel, 30% 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-92c664c986b14a21afe4765b9af714ec
Source dataset
uspto-grants-2012_01
Patent number
US08106191B2

Reaction notes

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