Hydrochloric Acid → (4-Hydroxymethyl-5-fluoro-thiazol-2-yl)-carbamic acid tert-butyl ester

HRID 2067999Notes

Reaction equation

HRID 2067999 reaction equation
[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[S:9][C:10]([F:18])=[C:11]([CH2:13]N(OC)C)[N:12]=1)([CH3:4])([CH3:3])[CH3:2].Cl[O-].[Na+].S1C=C(C=[O:29])N=C1.[BH4-].[Na+].Cl>C1COCC1.O>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[S:9][C:10]([F:18])=[C:11]([CH2:13][OH:29])[N:12]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 2763214Thiazole-4-carboxaldehydeHCID 4311764Sodium borohydrideHCID 23665760Sodium HypochloriteHCID 580550492-(tert-butoxycarbonylamino)-4-(N-methoxy-N-methyl-aminomethyl)-5-fluorothiazole2×

Product 1

HCID 86647350(4-Hydroxymethyl-5-fluoro-thiazol-2-yl)-carbamic acid tert-butyl esterYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of Intermediate 104: {5-Fluoro-4-[(methoxy-methyl-amino)-methyl]-thiazol-2-yl}-carbamic acid tert-butyl ester (7.5 g, 25.7 mmol) in THF (45 mL) and water (4.5 mL) was rapidly stirred and treated slowly dropwise with 6.15% sodium hypochlorite solution in water (Clorox™, 67 mL, 55 mmol). The resulting thiazole-4-carboxaldehyde was reduced in situ with sodium borohydride (0.5 g). The reaction was acidified with 2 N HCl (10 mL) and extracted with diethyl ether (2×50 mL). The extracts were dried with sodium sulfate and evaporated to leave an orange resin which purified by silica gel chromatography (80% EtOAc/hexane) to afford (4-hydroxymethyl-5-fluoro-thiazol-2-yl)-carbamic acid tert-butyl ester as a yellow foam (2.9 g, 45% yield).

Workup

  1. extractionextracted with diethyl ether (2×50 mL)
  2. dry with materialThe extracts were dried with sodium sulfate
  3. customevaporated
  4. customto leave an orange resin which
  5. custompurified by silica gel chromatography (80% EtOAc/hexane)

Sources & evidence

ORD record
ord-56ce5b0f06204018890156781e93cacd
Source dataset
uspto-grants-2012_10
Patent number
US08293919B2

Reaction notes

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