tert-butyl N-(2-oxoethyl)carbamate → HCID 86614262, compound

HRID 2099360Notes

Reaction equation

HRID 2099360 reaction equation
[Cl:1][C:2]1[CH:34]=[CH:33][C:5]([CH2:6][C@H:7]([C:9]([N:11]2[CH:16]3[CH2:17][CH2:18][CH:12]2[CH2:13][CH:14]([N:19]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:20]([N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])=[O:21])[CH2:15]3)=[O:10])[NH2:8])=[CH:4][CH:3]=1.O=[CH:36][CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C@@H:7]([NH:8][CH2:36][CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:9]([N:11]2[CH:16]3[CH2:17][CH2:18][CH:12]2[CH2:13][CH:14]([N:19]([CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]2)[C:20]([N:22]([CH2:23][CH3:24])[CH2:25][CH3:26])=[O:21])[CH2:15]3)=[O:10])=[CH:33][CH:34]=1

Participants

5

Reactant 3

HCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 5049666Sodium triacetoxyborohydrideHCID 68829063HCID 68829063, compound

Product 1

HCID 86614262HCID 86614262, compoundYield 45.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

0.24 g of the N-[8-(4-chloro-D-phenylalanyl)-8-azabicyclo[3.2.1]oct-3-yl]-N-cyclohexyl-N′,N′-diethylurea endo compound, obtained in step 1.5, is dissolved in 5 ml of dichloromethane under N2 in the presence of 0.10 g of tert-butyl N-(2-oxoethyl)carbamate and of 0.22 g of sodium triacetoxyborohydride. The reaction medium is stirred at ambient temperature for 16 h. After evaporation to dryness, 0.05 g of tert-butyl N-(2-oxoethyl)carbamate and 0.1 g of sodium triacetoxyborohydride are added, and stirring is maintained for 3 days. After the addition of 1 ml of methanol and 4 g of Dowex® 50X2 resin, the mixture is stirred for 1 h 30 min. After filtration and washing of the resin with tetrahydrofuran and methanol, the expected compound is released by adding a 1N solution of aqueous ammonia in methanol. The methanol is evaporated off, to give 0.14 g of tert-butyl (2-{[(1R)-1-(4-chlorobenzyl)-2-(3-{cyclohexyl[(diethylamino)carbonyl]amino}-8-azabicyclo[3.2.1]oct-8-yl)-2-oxoethyl]amino}ethyl)carbamate.

Workup

  1. customobtained in step 1.5
  2. customAfter evaporation to dryness, 0.05 g of tert-butyl N-(2-oxoethyl)carbamate and 0.1 g of sodium triacetoxyborohydride
  3. additionare added
  4. stirringstirring
  5. temperatureis maintained for 3 days
  6. additionAfter the addition of 1 ml of methanol and 4 g of Dowex® 50X2 resin
  7. stirringthe mixture is stirred for 1 h 30 min
  8. filtrationAfter filtration
  9. washwashing of the resin with tetrahydrofuran and methanol
  10. additionby adding a 1N solution of aqueous ammonia in methanol
  11. customThe methanol is evaporated off

Sources & evidence

ORD record
ord-7715afba7c51418290f0345d0569d82f
Source dataset
uspto-grants-2009_08
Patent number
US07569582B2

Reaction notes

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