Triethylamine → HCID 11825571, compound

HRID 1984767Notes

Reaction equation

HRID 1984767 reaction equation
[C:1]([O:5][C:6](=[O:19])[C:7]([NH:11]C(OC(C)(C)C)=O)([CH3:10])[CH2:8][OH:9])([CH3:4])([CH3:3])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(N(CC)CC)C.[CH3:39][O:40][C:41]1[CH:46]=[CH:45][C:44]([CH:47]([C:49]2[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][CH:50]=2)Cl)=[CH:43][CH:42]=1>C(OCC)C.CCO>[C:1]([O:5][C:6](=[O:19])[C:7]([NH:11][CH:47]([C:49]1[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][CH:50]=1)[C:44]1[CH:45]=[CH:46][C:41]([O:40][CH3:39])=[CH:42][CH:43]=1)([CH3:10])[CH2:8][OH:9])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 521998p-Toluenesulfonic acid monohydrateHCID 10706646bis(4-methoxyphenyl)chloromethaneHCID 111193112-[N-(tert-butoxycarbonyl)amino]-3-hydroxy-2-methylpropanoic acid tert-butyl ester

Product 1

HCID 11825571HCID 11825571, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of the alcohol 9 (100 mg, 0.36 mmol) in 2 mL of diethyl ether was added 1 eq of p-toluenesulfonic acid monohydrate (69 mg) dissolved in 6 mL of EtOH. The reaction mixture was concentrated under reduced pressure at 40° C., and the residue was dissolved in 6 mL of EtOH and concentrated again. This process was repeated 4 times, at which time no starting material was present on TLC analysis. The resulting white solid was suspended in 3 mL of CH2Cl2, and treated with 4.5 eq of triethylamine (0.23 mL) followed by 1 eq of bis(4-methoxyphenyl)chloromethane (95 mg). The reaction mixture was stirred for 1 hour at room temperature. The solution was then partitioned between 10 mL of EtOAc and 10 mL of H2O. The aqueous layer was extracted with 10 mL of EtOAc followed by the usual work up of the combined organic layers. Purification by silica gel column chromatography (20% EtOAc in hexane) provided the amino ester 12a as a colorless oil (107 mg, 73% from 9): 1H NMR (CDCl3) δ 1.17 (3H, s), 1.46 (9H, s), 3.35 (1H, d, J=11.2), 3.44 (1H, d, J=11.2), 3.76 (3H, s), 3.77 (3H, s), 4.82 (1H, s), 6.80-6.84 (4H, m), 7.27-7.31 (4H, m). Anal. (C23H31NO5)C,H,N.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure at 40° C.
  2. dissolutionthe residue was dissolved in 6 mL of EtOH
  3. concentrationconcentrated again
  4. customThe solution was then partitioned between 10 mL of EtOAc and 10 mL of H2O
  5. extractionThe aqueous layer was extracted with 10 mL of EtOAc
  6. customPurification by silica gel column chromatography (20% EtOAc in hexane)

Sources & evidence

ORD record
ord-0da8435ab3a94467b6482a5b28f5376c
Source dataset
uspto-grants-2009_06
Patent number
US07544715B2

Reaction notes

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