Methanol → HCID 69586011, compound

HRID 2213354Notes

Reaction equation

HRID 2213354 reaction equation
[C:1]([O:5][Li])(C)(C)[CH3:2].C1COCC1.[C:12]([O:16][C:17](=[O:33])[C:18]1[C:23]([F:24])=[CH:22][C:21]([NH:25][C:26]([O:28][CH:29]([CH3:31])[CH3:30])=[O:27])=[CH:20][C:19]=1[F:32])([CH3:15])([CH3:14])[CH3:13].CO.[NH4+:36].[Cl-]>CN(C=O)C.[Cl-].[Na+].O.C(Cl)Cl.O>[C:12]([O:16][C:17](=[O:33])[C:18]1[C:23]([F:24])=[CH:22][C:21]([N:25]2[CH2:31][CH:29]([CH2:30][NH:36][C:1](=[O:5])[CH3:2])[O:28][C:26]2=[O:27])=[CH:20][C:19]=1[F:32])([CH3:13])([CH3:15])[CH3:14]

Participants

10

Reactant 5

HCID 887MethanolHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 69585733HCID 69585733, compoundHCID 178506942HCID 178506942, compound

Product 1

HCID 69586011HCID 69586011, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

1.0 M t-BuOLi in THF (22.7 mL, 22.71 mmol) is added dropwise with stirring over ca. 5 min to a solution of 2,6-difluoro-4-isopropoxycarbonylamino-benzoic acid tert-butyl ester (2.39 g, 7.57 mmol) in DMF (4.84 mL) and MeOH (0.619 mL, 15.29 mmol) at 0° C. 1-(S)-2-Acetylamino-1-(chloromethyl)ethyl acetate (2.93 g, 15.14 mmol) is added on one portion to the reaction mixture at 0° C. The mixture is allowed to warm up to r.t. and then stirred for another 16 h. Satd. aq. NH4Cl (25 mL) is added, followed by addition of water (25 mL), brine (25 mL) and DCM (50 mL). The organic layer is separated, and aqueous phase is extracted with excess DCM (4×25 mL). The combined organic phase is dried over Na2SO4. The solvent is removed under vacuum. The crude material is purified by silica gel column chromatography (50–100% gradient of EtOAc—hexane) to afford the title compund. 1H NMR (300 MHz, CDCl3) δ 2.05 (s, 1H), 3.62–3.67 (m, 2H), 3.72–3.77 (m, 1H), 4.00(t, J=10.2 Hz, 1H) 4.74–4.83 (m, 1H), 6.08–6.13 (Br t, 1H) 7.14 (d, J=12.6 Hz, 2H).

Workup

  1. customThe organic layer is separated
  2. extractionaqueous phase is extracted with excess DCM (4×25 mL)
  3. dry with materialThe combined organic phase is dried over Na2SO4
  4. customThe solvent is removed under vacuum
  5. customThe crude material is purified by silica gel column chromatography (50–100% gradient of EtOAc—hexane)
  6. customto afford the title compund

Sources & evidence

ORD record
ord-cb86f3a1575846c2b462ed2ee5d17840
Source dataset
uspto-grants-2006_09
Patent number
US07105547B2

Reaction notes

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