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

HRID 1858538Notes

Reaction equation

HRID 1858538 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 8028TetrahydrofuranSolvent

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 THP (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 44A 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-0933cd8b380544afad54f6533cfd1121
Source dataset
uspto-grants-2000_11
Patent number
US06150527

Reaction notes

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