Acetic Acid → (R)-4-[3-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-2-methyl-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 655564Notes

Reaction equation

HRID 655564 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]([CH2:16][CH2:17][CH:18]=O)[CH2:10][C@H:9]1[CH3:20])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH2:22]1[C:24]2([CH2:29][CH2:28][NH:27][CH2:26][C@H:25]2[OH:30])[CH2:23]1.C(N(CC)CC)C.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]([CH2:16][CH2:17][CH2:18][N:27]2[CH2:28][CH2:29][C:24]3([CH2:22][CH2:23]3)[C@H:25]([OH:30])[CH2:26]2)[CH2:10][C@H:9]1[CH3:20])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 44541812(4S)-6-Azaspiro[2.5]octan-4-ol hydrochloride2×HCID 86638114(R)-2-Methyl-5-oxo-4-(3-oxo-propyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester

Product 1

HCID 67080649(R)-4-[3-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-2-methyl-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 0.418 g (1.47 mmol) of (R)-2-methyl-5-oxo-4-(3-oxo-propyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (example IC) in 10.5 ml dichloromethane was slowly added to a suspension of 0.241 g (1.47 mmol, 1 eq.) of (S)-6-aza-spiro[2.5]octan-4-ol hydrochloride (intermediate 2), 0.205 ml (1.47, 1 eq.) of triethylamine, 0.168 ml (2.94 mmol, 2 eq.) of acetic acid and 0.353 g (1.62 mmol, 1.1 eq.) of sodium triacetoxyborohydride in 55 ml dichloromethane. After 30 min, the reaction mixture was slowly added to a solution of sat. aq. sodium hydrogencarbonate, followed by extraction with dichloromethane (3 times). The organic phases were washed with a solution of sat. aq. sodium hydrogencarbonate and with 10% aq. sodium chloride solution. The combined organic phases were dried over Na2SO4 and evaporated to give 0.541 g (88%) of the title compound as white foam. MS: 396.3 (MH+).

Workup

  1. extractionfollowed by extraction with dichloromethane (3 times)
  2. washThe organic phases were washed with a solution of sat. aq. sodium hydrogencarbonate and with 10% aq. sodium chloride solution
  3. dry with materialThe combined organic phases were dried over Na2SO4
  4. customevaporated

Sources & evidence

ORD record
ord-e95b0626cddb485083a1729c71e60644
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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