Sodium Bicarbonate → 4-(1-Amino-2,2,2-trifluoro-ethyl)-4-cyclopropylmethyl-cyclohexanol

HRID 1948149Notes

Reaction equation

HRID 1948149 reaction equation
[CH:1]1([CH2:4][C:5]2([CH:15]([NH:20]S(C(C)(C)C)=O)[C:16]([F:19])([F:18])[F:17])[CH2:14][CH2:13][C:8]3(OCC[O:9]3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.C(=O)(O)[O-].[Na+].[BH4-].[Na+]>C(O)(=O)C.C(O)C>[NH2:20][CH:15]([C:5]1([CH2:4][CH:1]2[CH2:3][CH2:2]2)[CH2:6][CH2:7][CH:8]([OH:9])[CH2:13][CH2:14]1)[C:16]([F:17])([F:18])[F:19]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 670727082-Methyl-propane-2-sulfinic acid [1-(8-cyclopropylmethyl-1,4-dioxa-spiro[4.5]dec-8-yl)-2,2,2-trifluoro-ethyl]-amide

Product 1

HCID 670729054-(1-Amino-2,2,2-trifluoro-ethyl)-4-cyclopropylmethyl-cyclohexanol

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent

Procedure

A solution of 2-methyl-propane-2-sulfinic acid [1-(8-cyclopropylmethyl-1,4-dioxa-spiro[4.5]dec-8-yl)-2,2,2-trifluoro-ethyl]-amide (20, 1.00 g, 2.52 mmol) in 80% acetic acid (10 mL) was heated in a microwave oven for 10 min at 130° C. Then, the reaction mixture was slowly dropped into cold saturated sodium bicarbonate solution (150 mL), stirred for 30 min at room temperature and extracted three times with dichloromethane. The combined organic layers were dried over magnesium sulphate, filtered, and concentrated in vacuo to give the crude ketone, which was taken up in ethanol (20 mL), cooled to 0° C. and treated with sodium borohydride (190 mg, 5.03 mmol, 2.0 eq.). After the reaction went to completion, the mixture was poured onto water (20 mL) and extracted three times with dichloromethane. The organic layers were concentrated in vacuo and the residue was dissolved in a mixture of 2-propanol (15 mL) and 6N aqueous hydrochloric acid (5 mL). After stirring overnight at room temperature, another 5 mL of 6N aqueous hydrochloric acid were added and the mixture was warmed to 50° C. for 1 h. The reaction mixture was concentrated in vacuo and lyophilized twice from water to give the title compound (21) as racemic mixture of diastereoisomers as its hydrochloride. Rt=0.73 min, 0.82 min (Method B). Detected mass: 252.3 (M+H+).

Workup

  1. extractionextracted three times with dichloromethane
  2. dry with materialThe combined organic layers were dried over magnesium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give the crude ketone, which
  6. temperaturecooled to 0° C.
  7. additionthe mixture was poured onto water (20 mL)
  8. extractionextracted three times with dichloromethane
  9. concentrationThe organic layers were concentrated in vacuo
  10. dissolutionthe residue was dissolved in a mixture of 2-propanol (15 mL) and 6N aqueous hydrochloric acid (5 mL)
  11. stirringAfter stirring overnight at room temperature
  12. additionanother 5 mL of 6N aqueous hydrochloric acid were added
  13. temperaturethe mixture was warmed to 50° C. for 1 h
  14. concentrationThe reaction mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-ec20960f2eec4af289b3d503e635a34c
Source dataset
uspto-grants-2013_03
Patent number
US08399482B2

Reaction notes

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