Water → [4-(Benzothiazole-2-carbonyl)-cyclohexyl]-carbamic acid tert-butyl ester

HRID 1012912

Reaction equation

HRID 1012912 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Li]CCCC.[C:15]([O:19][C:20](=[O:34])[NH:21][C@H:22]1[CH2:27][CH2:26][C@H:25]([C:28](=[O:33])N(OC)C)[CH2:24][CH2:23]1)([CH3:18])([CH3:17])[CH3:16].O>C1COCC1>[C:15]([O:19][C:20](=[O:34])[NH:21][CH:22]1[CH2:23][CH2:24][CH:25]([C:28]([C:2]2[S:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)=[O:33])[CH2:26][CH2:27]1)([CH3:18])([CH3:16])[CH3:17]

Participants

6

Reactant 4

HCID 962WaterHCID 7222BenzothiazoleHCID 178418339ButyllithiumHCID 178502731HCID 178502731, compound

Product 1

HCID 67317166[4-(Benzothiazole-2-carbonyl)-cyclohexyl]-carbamic acid tert-butyl esterYield 82.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of benzothiazole (675 mg, 0.55 ml, 5 mmol) in THF (20 ml) at −78° C. was added dropwise n-BuLi (2.5M in Hex, 2 ml) such that the temperature did not exceed −70° C. The brown solution was stirred at this temperature for 15 min before dropwise addition of a solution of [trans-4-(methoxy-methyl-carbamoyl)-cyclohexyl]-carbamic acid tert-butyl ester (716 mg, 2.5 mmol, prepared according to WO 03/053933) in THF (2 ml). The temperature was kept below −70° C. The brown solution was then gradually allowed to reach RT (over 3 h). Mixture was poured into water and extracted with EtOAc. The combined organic extracts were washed with brine and dried over MgSO4 and concentrated under reduced pressure. The residue was purified by chromatography over SiO2 (Hex/EtOAc 4:1 then DCM). The relevant fractions were pooled, evaporated under reduced pressure, digested with Hex and filtered to give 740 mg (82%) of [4-(benzothiazole-2-carbonyl)-cyclohexyl]-carbamic acid tert-butyl ester.

Workup

  1. customdid not exceed −70° C
  2. customwas kept below −70° C
  3. customto reach RT
  4. custom(over 3 h)
  5. extractionextracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by chromatography over SiO2 (Hex/EtOAc 4:1
  10. customevaporated under reduced pressure
  11. filtrationfiltered

Sources & evidence

ORD record
ord-35a01e6be0c24725a8d37793c2468181
Source dataset
uspto-grants-2011_07
Patent number
US07981886B2

Linked notes

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