Sodium Hydroxide → HCID 15454894, compound

HRID 2287519Notes

Reaction equation

HRID 2287519 reaction equation
[NH2:1][C@H:2]1[C@@H:6]([C:7]([O:9][CH3:10])=[O:8])[C@@H:5]([CH3:11])[N:4]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C@H:3]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[CH:28]([C:31]1[CH:32]=[CH:33][C:34]([O:39][CH3:40])=[C:35]([CH:38]=1)[CH:36]=O)([CH3:30])[CH3:29].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>C(Cl)Cl>[CH2:15]([O:14][C:12]([N:4]1[C@H:5]([CH3:11])[C@H:6]([C:7]([O:9][CH3:10])=[O:8])[C@H:2]([NH:1][CH2:36][C:35]2[CH:38]=[C:31]([CH:28]([CH3:30])[CH3:29])[CH:32]=[CH:33][C:34]=2[O:39][CH3:40])[C@@H:3]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:13])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride2×HCID 70095025-ISOPROPYL-2-METHOXYBENZALDEHYDEHCID 15454895HCID 15454895, compound

Product 1

HCID 15454894HCID 15454894, compoundYield 126.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (2S*,3S*,4R*,5R*)-3-amino-1-benzyloxycarbonyl-4-methoxycarbonyl-5-methyl-2-phenylpyrrolidine (0.93 g, 2.52 mmol) in dry CH2Cl2 (20 ml) was added a solution of 5-isopropyl-2-methoxybenzaldehyde (0.56 g, 3.15 mmol) in dry CH2Cl2 (5 ml) at room temperature. To this was added NaBH(OAc)3 (0.80 g, 3.78 mmol) portionwise at room temperature. The added NaBH(OAc)3 dissolved gradually with stirring at room temperature. After stirring for 1.5 hours at room temperature, the reaction mixture was basified to pH 10-11 by adding 10% NaOH aq. solution with ice-cooling. The layers were separated, and the aqueous layer was extracted with CHCl3 (×3). The combined CH2Cl2 layer and CHCl3 extracts were washed with sat. NaCl aq. solution (×1), dried (Na2SO4 --K2CO3), and concentrated in vacuo to give a yellow viscous oil (1.69 g). This was chromatographed over SiO2 (Merck Kieselgel 60, 20 g). Elution with n-hexane-AcOEt (30: 1) followed by CH2Cl2 --MeOH (200:1) gave title compound (1.36 g, quant.) as a pale yellow viscous oil: IRmax (film): 3350(w), 1735(s), 1700(vs), 1487(s), 1290(s), 1250(s), 1030(s), 810(s), 735(s), 700(s) cm-1 ; 1H-NMR δ: 7.50-7.15(m, 10H), 7.03(dd, J=8.4, 2.2 Hz, 1H), 6.96(d, J=2.2 Hz, 1H), 6.70(d, J=8.4 Hz, 1H), 5.15(br.d, J=7.7 Hz, 1H), 5.03(br.s, 2H), 4.22-4.06(m, 1H), 3.84-3.58(m, 3H), 3.71(s, 3H), 3.64(s, 3H), 2.90-2.58 (m, 2H), 1.61(br.d, J=5.5 Hz, 3H), 1.19(d, J=7.0 Hz, 6H) ppm.

Workup

  1. stirringAfter stirring for 1.5 hours at room temperature
  2. temperaturecooling
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with CHCl3 (×3)
  5. washThe combined CH2Cl2 layer and CHCl3 extracts were washed with sat. NaCl aq. solution (×1)
  6. dry with materialdried (Na2SO4 --K2CO3)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7f82d5bcabca4506af6138b854720dc2
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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