Hydrochloric Acid → Boc-O-ethyl-L-tyrosine

HRID 1369165Notes

Reaction equation

HRID 1369165 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(OCC)(O[CH2:25][CH3:26])(=O)=O.C(OCC)(=O)C.Cl>[OH-].[Na+]>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:25][CH3:26])=[CH:15][CH:16]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6163Diethyl SulfateHCID 8857Ethyl AcetateHCID 117439L-Tyrosine, N-(1,1-dimethylethoxy)carbonyl-2×

Product 1

HCID 7017903Boc-O-ethyl-L-tyrosine

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

N-t-butoxycarbonyl-L-tyrosine (II, EXAMPLE 1, (235 g, 835 mmol) is dissolved in sodium hydroxide (4N, 705 mL) at 20-25°. Diethyl sulfate (210 mL, 1.60 mol) is added over 15-20 min. The reaction mixture is stirred for 2 hr, then it is cooled with ice-bath (internal temperature around 15°). Ethyl acetate (1400 mL) is added, followed by slow addition of hydrochloric acid (3N, 1410 mL) for 1 hr. The ethyl acetate layer is separated, and the aqueous layer is extracted with ethyl acetate (1400 mL). The ethyl acetate phase is concentrated to about 200 mL, then hexane (1600 mL) is added. The mixture is stirred in an ice-bath for 2 hr, filtered, washed with hexane (800 mL) in 3 portions. The precipitate is dried to give the title compound. The filtrate is concentrated, suspended in ethyl acetate/hexane (80/450 mL) for 2 hr, filtered and washed with hexane (250 mL) in 3 portions and dried to give additional title compound, NMR (MeOH-d4) δ7.11, 6.80, 4.22, 4.05, 3.08, 2.86 and 1.36; CMR δ175.4, 159.3, 157.8, 131.3, 130.4, 115.4, 80.5, 64.4, 56.4, 37.9, 28.7 and 15.2.

Workup

  1. temperatureit is cooled with ice-bath (internal temperature around 15°)
  2. customThe ethyl acetate layer is separated
  3. extractionthe aqueous layer is extracted with ethyl acetate (1400 mL)
  4. concentrationThe ethyl acetate phase is concentrated to about 200 mL
  5. additionhexane (1600 mL) is added
  6. stirringThe mixture is stirred in an ice-bath for 2 hr
  7. filtrationfiltered
  8. washwashed with hexane (800 mL) in 3 portions
  9. customThe precipitate is dried

Sources & evidence

ORD record
ord-5aafccb5b5314344b30bfb4eb46fd748
Source dataset
uspto-grants-2003_06
Patent number
US06576769B2

Reaction notes

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