Isopropyl Acetate → 2-Amino-1,2-diphenylethanol

HRID 132759Notes

Reaction equation

HRID 132759 reaction equation
[Br:1][CH:2]([CH2:6][CH2:7][N:8]1[C:12](=[O:13])[C:11]([CH3:15])([CH3:14])[N:10]([CH3:16])[C:9]1=[O:17])[C:3]([OH:5])=[O:4].[NH2:18][C@@H:19]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@@H:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[OH:21].C(OC(C)C)(=O)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OC)(C)(C)C>[Br:1][C@H:2]([CH2:6][CH2:7][N:8]1[C:12](=[O:13])[C:11]([CH3:15])([CH3:14])[N:10]([CH3:16])[C:9]1=[O:17])[C:3]([OH:5])=[O:4].[NH2:18][CH:19]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[OH:21]

Participants

7

Reactant 3

HCID 7915Isopropyl AcetateHCID 719819(1R,2S)-2-Amino-1,2-diphenylethanolHCID 11324242HCID 11324242, compound

Product 2

HCID 222432-Amino-1,2-diphenylethanolHCID 11168359HCID 11168359, compound

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
57.5 °C

Procedure

α-Bromo-3,4,4-trimethyl-2,5-dioxo-1-imidazolidinebutanoic acid (I) (111 g, 362.4 mmol) and (1R,2S)-(−)-2-amino-1,2-diphenylethanol (II) (the chiral amine, 75 g, 351 mmol, Aldrich) and tetrabutylammonium bromide (catalytic nucleophile, 2.4 g) were charged to a flask. I was obtained by/from Aerojet Fine Chemicals (a Division of Gencorp, Rancho Cordova, Calif.). To this was added 3 L of a 1:1 mixture of i-propyl acetate (i-PrOAc) and methyl t-butyl ether (MTBE). The resulting slurry was heated to 55-60° C. for 24 to 48 h. Reaction was deemed complete when the ratio of the diastereomers was ≧94:6 (R:S). The reaction was cooled to room temperature and the diastereomeric salt, (R)-α-bromo-3,4,4-trimethyl-2,5-dioxo-1-imidazolidinebutanoic acid, [R-(R*,S*)]-β-amino-α-phenylbenzeneethanol salt (1:1) (IA), was isolated by filtration. The product cake was washed with 850 mL of MTBE. The MTBE wet product cake was suspended in 1800 mL of MTBE. Water, 1800 mL was added. The pH of the aqueous phase was adjusted to between 1 and 2 with methanesulfonic acid (˜23 mL). The phases were separated and the lower aqueous phase was extracted with MTBE (3×1L). The combined organic phases were washed with water (250 mL). The product, (R)-α-bromo-3,4,4-trimethyl-2,5-dioxo-1-imidazolidinebutanoic acid (IB)was used directly in the next step without isolation. In process yield and quality was 101.0 g, 93.0 M%, 87.4% ee (enantiomeric excess). IB: 1H NMR (CDCl3): δ(ppm)=4.30 (m, 1H), 3.72 (m, 2H), 2.96 (s, 3 H), 2.48 (m, 1H), 2.27 (m, 1H), 1.39 (s, 6H). 13C NMR (CDCl3): δ (ppm)=176.7, 172.2, 155.2, 61.4, 41.7, 36.6, 33.2, 24.4, 21.9, 21.9. IR (KBr): ν (cm−1)=3000 (br), 1740 (s), 1680 (s), 1450 (br), 1250 (s).

Workup

  1. additionTo this was added
  2. customReaction
  3. temperatureThe reaction was cooled to room temperature

Sources & evidence

ORD record
ord-02bdcb72c95742708d81979c4a6c7a51
Source dataset
uspto-grants-2008_06
Patent number
US07388098B2

Reaction notes

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