Sodium Hydroxide → HCID 15454947, compound

HRID 2287515Notes

Reaction equation

HRID 2287515 reaction equation
[NH2:1][C@H:2]1[C@H:6]([CH2:7][OH:8])[C@@H:5]([CH3:9])[N:4]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[C@H:3]1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[CH:26]([C:29]1[CH:30]=[CH:31][C:32]([O:37][CH3:38])=[C:33]([CH:36]=1)[CH:34]=O)([CH3:28])[CH3:27].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>C(Cl)Cl>[CH2:13]([O:12][C:10]([N:4]1[C@H:5]([CH3:9])[C@H:6]([CH2:7][OH:8])[C@H:2]([NH:1][CH2:34][C:33]2[CH:36]=[C:29]([CH:26]([CH3:28])[CH3:27])[CH:30]=[CH:31][C:32]=2[O:37][CH3:38])[C@@H:3]1[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)=[O:11])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride2×HCID 70095025-ISOPROPYL-2-METHOXYBENZALDEHYDEHCID 70304033HCID 70304033, compound

Product 1

HCID 15454947HCID 15454947, compoundYield 148.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (2S*,3S*,4S*,5R*)-3-amino-1-benzyloxycarbonyl-4-hydroxymethyl-5-methyl-2-phenylpyrrolidine (0.61 g, 1.79 mmol) in dry CH2Cl2 (14 ml) was added a solution of 5-isopropyl-2-methoxybenzaldehyde (0.40 g, 2.24 mmol) in dry CH2Cl2 (2 ml) at room temperature. To this was then added NaBH(OAc)3 (0.57 g, 2.69 mmol) portionwise at room temperature. The added NaBH(OAc)3 dissolved gradually with stirring at room temperature. After stirring for 3 hours at room temperature, the reaction mixture was basified to pH 10-11 with 10% NaOH aq. solution. The mixture was separated, and the aqueous layer was extracted with CH2Cl2 (×3). The combined CH2Cl2 solution was washed with sat. NaCl aq. solution (×1), dried (K2CO3), and concentrated in vacuo to give a yellow oil (1.34 g). This was chromatographed over SiO2 (Merck Kieselgel 60, 20 g). Elution with n-hexane-AcOEt (30:1) followed by CH2Cl2 --MeOH (400:1→200:1) gave title compound (0.70 g, 78%) as a viscous pale yellow oil: IRmax (film): 3330(s), 1700(s), 1610(m), 1500(s), 1250(s), 1110(s), 1030(s), 815(s), 770(s), 738(s), 700(s) cm- ; 1H-NMR δ: 7.45-7.16(m, 9H), 7.05(dd, J=8.4, 1.8 Hz, 1H), 7.02(br.s, 1H), 6.88(d, J=1.8 Hz, 1H), 6.71(d, J=8.4 Hz, 1H), 5.33-4.93(m, 3H), 3.97-3.65(m, 3H), 3.81(d, J=12.1 Hz, 1H), 3.72(d,J=12.1 Hz, 1H), 3.67(s, 3H), 3.53-3.35(m, 1H), 3.38(dd,J=11.5, 7.9 Hz), 2.79 (sep, J=7.0 Hz, 1H), 2.17-1.98(m, 1H), 1.56(br.s, 4H), 1.18(d, J=7.0 Hz, 6H) ppm.

Workup

  1. customportionwise at room temperature
  2. stirringAfter stirring for 3 hours at room temperature
  3. customThe mixture was separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (×3)
  5. washThe combined CH2Cl2 solution was washed with sat. NaCl aq. solution (×1)
  6. dry with materialdried (K2CO3)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4b8ed45326ae49e29bfae8838cc0ad0d
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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