Water → HCID 67377819, compound

HRID 1509847Notes

Reaction equation

HRID 1509847 reaction equation
[F:1][C:2]1[C:11]([CH:12]=O)=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([O:14][CH3:15])=[N:9]2)=[CH:4][CH:3]=1.[C:16]([O:20][C:21](=[O:44])[NH:22][C@@H:23]1[CH2:28][CH2:27][C@@H:26]([CH2:29]S(C2N(C3C=CC=CC=3)N=NN=2)(=O)=O)[O:25][CH2:24]1)([CH3:19])([CH3:18])[CH3:17].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.O>COCCOC.CC(=O)OCC>[C:16]([O:20][C:21](=[O:44])[NH:22][C@@H:23]1[CH2:28][CH2:27][C@@H:26](/[CH:29]=[CH:12]/[C:11]2[C:2]([F:1])=[CH:3][CH:4]=[C:5]3[C:10]=2[N:9]=[C:8]([O:14][CH3:15])[CH:7]=[CH:6]3)[O:25][CH2:24]1)([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 4

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 67366724HCID 67366724, compoundHCID 86658142HCID 86658142, compound

Product 1

HCID 67377819HCID 67377819, compound

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-60 °C

Procedure

A mixture of 7-fluoro-2-methoxy-quinoline-8-carbaldehyde (5 g, 24.36 mmol; prepared according to WO 2008/126024) and (3R,6S)-[6-(1-phenyl-1H-tetrazole-5-sulfonylmethyl)-tetrahydro-pyran-3-yl]-carbamic acid tert-butyl ester (10.32 g, 24.36 mmol, prepared according to WO 2006/032466) in DME (104 mL) was cooled to −60° C. A solution of LiHMDS (1M in THF, 42 mL) was added drop wise over 30 min. The reaction was stirred 1 hour at this temperature before warming slowly to rt. Water (80 mL) and EA (80 mL) were added. The two layers were decanted and the aq. layer was extracted twice with EA (2×100 mL). The combined org. layers were washed with brine (100 mL), dried over MgSO4 and concentrated to dryness. The residue (10.5 g) was carried on without further purification. The analytical data were obtained by trituration of a small portion of the crude in diethyl ether.

Workup

  1. temperaturebefore warming slowly to rt
  2. customThe two layers were decanted
  3. extractionthe aq. layer was extracted twice with EA (2×100 mL)
  4. washlayers were washed with brine (100 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated to dryness
  7. customThe residue (10.5 g) was carried on without further purification
  8. customThe analytical data were obtained by trituration of a small portion of the crude in diethyl ether

Sources & evidence

ORD record
ord-d5b355de1f8c42568055fd2bbfc0fd2e
Source dataset
uspto-grants-2012_07
Patent number
US08211890B2

Reaction notes

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