Water → HCID 86653602, compound

HRID 1892010Notes

Reaction equation

HRID 1892010 reaction equation
[N:1]([CH2:4][CH:5]1[CH2:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=2)([CH3:11])[C:8]([C:23]([O:25][CH3:26])=[O:24])=[CH:7][CH2:6]1)=[N+]=[N-].O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[C:54](OC(=O)C)(=[O:56])[CH3:55]>C1COCC1.ClCCl.CN(C1C=CN=CC=1)C>[C:54]([NH:1][CH2:4][CH:5]1[CH2:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=2)([CH3:11])[C:8]([C:23]([O:25][CH3:26])=[O:24])=[CH:7][CH2:6]1)(=[O:56])[CH3:55]

Participants

9

Reactant 5

HCID 962WaterHCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86653601HCID 86653601, compound

Product 1

HCID 86653602HCID 86653602, compoundYield 123.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl (4RS,6RS)-4-(azidomethyl)-6-(4-chloro-3-(trifluoromethyl)phenyl)-6-methylcyclohex-1-enecarboxylate (21 mg, 0.054 mmol) in THF (0.5 mL) was treated with water (25 μL, 1.388 mmol) followed by triphenylphosphine (15.62 mg, 0.060 mmol). The resulting mixture was stirred at rt for 21.5 h and then concentrated under vacuum to yield a residue. The residue was dissolved in dichloromethane (0.5 mL) and the resulting solution was treated with triethylamine (0.030 mL, 0.217 mmol), dmap (3.31 mg, 0.027 mmol) and acetic anhydride (10.22 μL, 0.108 mmol). The resulting mixture was stirred at rt for 2 h and then concentrated under vacuum to yield a residue. This residue was purified by column chromatography on silica gel, eluting with 60-100% ethyl acetate-hexanes, to provide methyl (4RS,6RS)-4-(acetamidomethyl)-6-(4-chloro-3-(trifluoro-methyl)phenyl)-6-methylcyclohex-1-enecarboxylate (27 mg, estimated 68% yield), which was used in the next step without further purification despite being contaminated with about 45% by weight of triphenylphosphine oxide.

Workup

  1. concentrationconcentrated under vacuum
  2. customto yield a residue
  3. stirringThe resulting mixture was stirred at rt for 2 h
  4. concentrationconcentrated under vacuum
  5. customto yield a residue
  6. customThis residue was purified by column chromatography on silica gel
  7. washeluting with 60-100% ethyl acetate-hexanes

Sources & evidence

ORD record
ord-275c16f916d84de182956f7e92cc5d8b
Source dataset
uspto-grants-2013_08
Patent number
US08507559B2

Reaction notes

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