Sodium Bicarbonate → 1-(3,4-Dichloro-phenyl)-4-[(S)-3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-1-hydroxymethyl-propyl]-[1,4]diazepan-5-one

HRID 1096202Notes

Reaction equation

HRID 1096202 reaction equation
C[O:2][C:3](=O)[C@@H:4]([N:16]1[C:22](=[O:23])[CH2:21][CH2:20][N:19]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=2)[CH2:18][CH2:17]1)[CH2:5][CH2:6][N:7]1[CH2:14][CH2:13][C:10]2([CH2:12][CH2:11]2)[C@H:9]([OH:15])[CH2:8]1.[Li+].[BH4-].OS([O-])(=O)=O.[K+].C([O-])(O)=O.[Na+]>>[Cl:31][C:26]1[CH:25]=[C:24]([N:19]2[CH2:20][CH2:21][C:22](=[O:23])[N:16]([C@H:4]([CH2:3][OH:2])[CH2:5][CH2:6][N:7]3[CH2:14][CH2:13][C:10]4([CH2:12][CH2:11]4)[C@H:9]([OH:15])[CH2:8]3)[CH2:17][CH2:18]2)[CH:29]=[CH:28][C:27]=1[Cl:30]

Participants

5

Reactant 4

HCID 516892Sodium BicarbonateHCID 516920Potassium bisulfateHCID 4148881Lithium borohydride3×HCID 59159299(S)-2-[4-(3,4-Dichloro-phenyl)-7-oxo-[1,4]diazepan-1-yl]-4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyric Acid methyl ester

Product 1

HCID 451007151-(3,4-Dichloro-phenyl)-4-[(S)-3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-1-hydroxymethyl-propyl]-[1,4]diazepan-5-oneYield 75.2%

Conditions

Temperature
0 °C

Procedure

A solution of 0.180 g (0.37 mmol) of (S)-2-[4-(3,4-dichloro-phenyl)-7-oxo-[1,4]diazepan-1-yl]-4-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyric acid methyl ester in 4 ml of ETOH was treated at 0° C. with 0.017 g (0.74 mmol) of LiBH4. The reaction was stirred 10 min at 0° C. and 22 h at RT, cooled (0° C.) and treated with 0.009 g (0.37 mmol) of LiBH4 and after 5 h again cooled (0° C.) and treated with 0.009 g (0.37 mmol) of LiBH4. After 1 h at RT, the reaction was cooled (0° C.), acidified with 10% aq. KHSO4 solution and then basified with sat. aq NaHCO3 solution and extracted with EtOAc (3×). The organic phases were washed with aq. 10% NaCl solution, dried over Na2SO4 evaporated and purified by flash silica gel column (CH2Cl2:MeOH 95:5 to 9:1) to yield 0.127 g (75%) of the title compound as white foam. MS: 456.2 (MH+, 2Cl).

Workup

  1. temperaturecooled (0° C.)
  2. temperatureagain cooled (0° C.)
  3. waitAfter 1 h at RT
  4. temperaturethe reaction was cooled (0° C.)
  5. extractionextracted with EtOAc (3×)
  6. washThe organic phases were washed with aq. 10% NaCl solution
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. custompurified by flash silica gel column (CH2Cl2:MeOH 95:5 to 9:1)

Sources & evidence

ORD record
ord-185aa2e7285c45f493c35af05996952c
Source dataset
uspto-grants-2012_03
Patent number
US08138175B2

Reaction notes

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