4-Methoxybenzyl alcohol → (2S,3R)-3-Allyl-1-(tert-butyl-dimethyl-silanyl)-4-oxo-azetidine-2-carboxylic acid 4-methoxy-benzyl ester

HRID 1783425Notes

Reaction equation

HRID 1783425 reaction equation
[CH2:1]([C@H:4]1[C:7](=[O:8])[N:6]([Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])[C@@H:5]1[C:16]([OH:18])=[O:17])[CH:2]=[CH2:3].CCN=C=NCCCN(C)C.Cl.[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37]O)=[CH:35][CH:34]=1>CN(C1C=CN=CC=1)C.ClCCl>[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][O:17][C:16]([C@@H:5]2[C@@H:4]([CH2:1][CH:2]=[CH2:3])[C:7](=[O:8])[N:6]2[Si:9]([C:12]([CH3:13])([CH3:14])[CH3:15])([CH3:10])[CH3:11])=[O:18])=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 77384-Methoxybenzyl alcoholHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 14586689(2S,3R)-3-Allyl-1-(tert-butyl-dimethyl-silanyl)-4-oxo-azetidine-2-carboxylic acid

Product 1

HCID 57589741(2S,3R)-3-Allyl-1-(tert-butyl-dimethyl-silanyl)-4-oxo-azetidine-2-carboxylic acid 4-methoxy-benzyl esterYield 49%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 900 mg of crude compound 57 (3.34 mmol) above, EDC hydrochloride salt (1.34 g, 7.01 mmol), DMAP (83 mg, 0.67 mmol) and 4-methoxybenzyl alcohol (1.40 g, 10.1 mmol) in dichloromethane (9 mL) was stirred at room temperature overnight. The solvent was removed in vacuo. The residue was dissolved with ethyl acetate, washed with 5% aqueous KHSO4, water (×2) and brine (×1). The organic layer was dried over Na2SO4, then concentrated to yield the crude 58 with LC purity: 60%. Purification by ISCO silica gel column using 0-20% AcOEt in Hexanes afforded 630 mg of compound 58 (49% yield, 81% purity): 1HNMR (300 MHz, CDCl3): 0.13 (s, 3H), 0.32 (s, 3H), 0.95 (s, 9H), 2.56 (m, 2H), 3.43 (m, 1H), 3.81 (d, J=2.60 Hz, 1H), 3.82 (s, 3H), 4.67 (s, 2H), 5.17 (m, 2H), 5.72 (m, 1H), 6.94 (d, 2H), 7.34 (d, 2H). Anal. C21H31NO4Si, Mol. Wt.: 389.56. Found: ESI-MS: 390.0 (M+H)+.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved with ethyl acetate
  3. washwashed with 5% aqueous KHSO4, water (×2) and brine (×1)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customto yield the crude 58 with LC purity: 60%
  7. customPurification by ISCO silica gel column

Sources & evidence

ORD record
ord-bd3714c40d89410691f4cfe1b050b370
Source dataset
uspto-grants-2009_03
Patent number
US07501404B2

Reaction notes

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